+publisher:"Georgia Tech" +contributor:("Nerem, Robert")

Georgia Tech

1. Rathan, Swetha. Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification.

Degree: PhD, Chemical and Biomolecular Engineering, 2016, Georgia Tech

URL: http://hdl.handle.net/1853/58144

► Calcific aortic valve (AV) disease is a strong risk factor for cardiovascular related deaths and is a significant source of mortality worldwide, with the number… (more)

▼ Calcific aortic valve (AV) disease is a strong risk factor for cardiovascular related deaths and is a significant source of mortality worldwide, with the number of patients requiring AV surgery expected to increase from 250,000 to 850,000 by 2050. However, the molecular mechanisms underlying AV disease have not been well studied or understood. Further, identification of biomarkers that can be used to detect early stage AV disease is also understudied but vital to successfully preventing and/or treating AV disease. It was hypothesized that sclerosis, inflammation and calcification preferentially occurs in the fibrosa compared to the ventricularis due to differential gene expression and oscillatory shear stress. Freshly isolated porcine AV leaflets and an ex vivo shear stress bioreactor was used to test this hypothesis. The low magnitude oscillatory shear stress (OS) appeared to predispose fibrosa to side-dependent calcification via increasing collagen turnover (Col1a1), and thickening of the extracellular matrix (ECM) (fibrosis) and decreasing the expression of genes that protect endothelial function (Klf4 and Enos). The unidirectional pulsatile shear, LS, however, preserved the ECM and gene expression in the ventricularis. The involvement of miRNAs in OS mediated AV pathogenesis was also investigated in a shear- and side-dependent manner. The miR-214 was found to play a role in this OS induced pathogenesis in fibrosa but not ventricularis. Using an ex vivo miRNA silencing protocol, anti-miRNA was delivered to both endothelial and interstitial cells of the AV tissue without compromising the cell viability. Silencing of miR-214 showed that the OS induced pathology in the fibrosa is likely to be mediated via miR-214, klf4 and Tgfβ1 dependent pathway that can lead to AV fibrosis, endothelial-to-mesenchymal transition and eventually sclerosis. The miR-214, however, did not play a role in shear-induced inflammation and calcification. The miR-214, as such, is likely to play a key role in the early onset of side- and shear- dependent AV disease and has a potential to serve as a disease biomarker. Further, an ex vivo AV calcification model was also developed to understand the role of endogenous pro- and anti-calcification factors, such as inorganic pyrophosphate, orthophosphate, and alkaline phosphatase. The functional studies carried out in this dissertation aim to link the mechanosensitive miRNAs to the genes involved in inflammation, endothelial-to-mesenchymal transition, and cell apoptosis etc, which eventually causes AV leaflets to calcify. Thus improved understanding of AV disease mechanisms under different hemodynamic conditions will enable us to improve the design of tissue-engineered valves and develop non-surgical treatment options. Advisors/Committee Members: Yoganathan, Ajit P. (advisor), Jo, Hanjoong (committee member), Taylor, W. Robert (committee member), Champion, Julie A. (committee member), Nerem, Robert M. (committee member).

Subjects/Keywords: Aortic valve; Hemodynamics; Mechanobiology; MicroRNA; Calcification

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APA (6^th Edition):

Rathan, S. (2016). Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58144

Chicago Manual of Style (16^th Edition):

Rathan, Swetha. “Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification.” 2016. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/58144.

MLA Handbook (7^th Edition):

Rathan, Swetha. “Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification.” 2016. Web. 21 Apr 2021.

Vancouver:

Rathan S. Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/58144.

Council of Science Editors:

Rathan S. Aortic valve mechanobiology- role of altered hemodynamics in mediating aortic valve inflammation and calcification. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/58144

Georgia Tech

2. Kumar, Vivek Ashok. Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials.

Degree: PhD, Biomedical Engineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/45869

► For small diameter (<6 mm) blood vessel replacements, lack of collaterals and vascular disease preclude homografts; while synthetic analogs, ePTFE, expanded polytetrafluoroethylene, and PET, polyethyleneterephathalate,… (more)

Subjects/Keywords: Rat aortic interposition; Rat tail tendon; Vascular; Elastin; Collagen; Soft tissue; Blood vessels; Tissue engineering; Regenerative medicine; Arterial grafts; Tissue scaffolds

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APA (6^th Edition):

Kumar, V. A. (2011). Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45869

Chicago Manual of Style (16^th Edition):

Kumar, Vivek Ashok. “Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/45869.

MLA Handbook (7^th Edition):

Kumar, Vivek Ashok. “Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials.” 2011. Web. 21 Apr 2021.

Vancouver:

Kumar VA. Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/45869.

Council of Science Editors:

Kumar VA. Design and evaluation of scaffolds for arterial grafts using extracellular matrix based materials. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/45869

Georgia Tech

3. Fernandez Esmerats, Joan. The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2018, Georgia Tech

URL: http://hdl.handle.net/1853/62206

► Calcific Aortic Valve Disease (CAVD), characterized by aortic valve (AV) stenosis and insufficiency (regurgitation), is a major cause of cardiac-related deaths worldwide, especially in the… (more)

▼ Calcific Aortic Valve Disease (CAVD), characterized by aortic valve (AV) stenosis and insufficiency (regurgitation), is a major cause of cardiac-related deaths worldwide, especially in the aging population in advanced countries. Once developed, it is treated mainly with AV repair or replacement by surgical or transcathether methods; however, there are currently no pharmacological treatment options for these patients. This is largely due to a relative paucity in molecular mechanistic understanding of the disease. CAVD was once thought to be a passive degenerative disease, but overwhelming evidence demonstrates that it is actively regulated by cellular and molecular pathways that lead to AV inflammation, sclerosis (thickening and fibrosis), and calcific lesions. MicroRNAs (miRNAs) are a large class of evolutionarily conserved, noncoding RNAs which function as post-transcriptional regulators by interacting with the 3’ untranslated region (3’UTR) of specific target mRNAs in a sequence-specific manner. A single miRNA can typically target hundreds of mRNAs. These miRNAs negatively regulate gene expression through translational repression or mRNA cleavage, depending on the degree of complementarity. Flow-sensitive miRNAs have been mostly characterized in vitro however, their role in human disease has not been fully studied. Previous work in our laboratory has focused on identifying shear-sensitive and side-specific (ventricularis compared to fibrosa layers of the AV) miRNAs relevant to CAVD. To this end, we conducted two independent microRNA array studies. First, we isolated human aortic valve endothelial cells (HAVECs) from each side of the leaflet and exposed them to high-magnitude unidirectional laminar shear stress (LS) or low-magnitude oscillatory shear stress (OS) conditions for 24 hours to discover shear-sensitive miRNAs. Second, we isolated endothelial-enriched total RNAs from each side of the leaflet from porcine AVs to discover side-specific miRNAs. These studies allowed us to identify miR-181b and miR-483 as potential miRNAs for further studies. In Aim 1, we focused on studying shear-sensitive miR-181b. We showed that miR-181b was upregulated in OS conditions and that it regulates matrix metalloproteinases (MMP) activity in valvular endothelium. We conducted an in silico analysis combining predicted gene targets of miR-181b and shear-sensitive target genes from our in vitro HAVEC array and identified tissue inhibitor of metalloproteinases 3 (TIMP3) as a shear-sensitive target of miR-181b responsible for the role of miR-181b in extracellular matrix (ECM) degradation. Therefore, we showed that ECM degradation, a critical step in CAVD, might be mediated by the miR-181b/TIMP3 pathway. In Aim 2, we focused on studying the novel shear-sensitive miR-483-3p. We discovered that it regulated inflammation and endothelial-to-mesenchymal transition (EndMT) in HAVECs. In HAVECs we identified UBE2C as a novel shear-sensitive gene targeted by miR-483; which regulates endothelial inflammation and EndMT. Additionally, UBE2C exerts… Advisors/Committee Members: Jo, Hanjoong (advisor), Taylor, W. Robert (committee member), Nerem, Robert M. (committee member), Yoganathan, Ajit P. (committee member), Wilkinson, Keith D. (committee member), Garcia, Andres (committee member).

Subjects/Keywords: OS; miRNA; HAVECs; LS; TIMP3; UBE2C; HIF1A; pVHL; KLF2; Inflammation; Aortic valve; Calcification

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fernandez Esmerats, J. (2018). The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62206

Chicago Manual of Style (16^th Edition):

Fernandez Esmerats, Joan. “The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/62206.

MLA Handbook (7^th Edition):

Fernandez Esmerats, Joan. “The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease.” 2018. Web. 21 Apr 2021.

Vancouver:

Fernandez Esmerats J. The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/62206.

Council of Science Editors:

Fernandez Esmerats J. The role of flow-sensitive MiRNAs and UBE2C-dependent HIF1α pathway in calcific aortic valve disease. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/62206

4. Iyer, Gokulakrishnan Seshadri. Superoxide dismutase delivery and cardiac progenitor cell characterization for myocardial regeneration applications.

Degree: PhD, Biomedical Engineering, 2011, Georgia Tech

URL: http://hdl.handle.net/1853/42846

► Cardiovascular diseases are the leading cause of death throughout the world and various estimates predict that heart disease will remain the number one killer in… (more)

Subjects/Keywords: Myocardial infarction; Drug delivery; Cell therapy; Biomaterials; Antioxidants; Superoxide dismutase; Cardiac progenitor cells; Oxidative stress; Myocardium Regeneration; Biomedical materials; Cellular therapy

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APA (6^th Edition):

Iyer, G. S. (2011). Superoxide dismutase delivery and cardiac progenitor cell characterization for myocardial regeneration applications. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/42846

Chicago Manual of Style (16^th Edition):

Iyer, Gokulakrishnan Seshadri. “Superoxide dismutase delivery and cardiac progenitor cell characterization for myocardial regeneration applications.” 2011. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/42846.

MLA Handbook (7^th Edition):

Iyer, Gokulakrishnan Seshadri. “Superoxide dismutase delivery and cardiac progenitor cell characterization for myocardial regeneration applications.” 2011. Web. 21 Apr 2021.

Vancouver:

Iyer GS. Superoxide dismutase delivery and cardiac progenitor cell characterization for myocardial regeneration applications. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/42846.

Council of Science Editors:

Iyer GS. Superoxide dismutase delivery and cardiac progenitor cell characterization for myocardial regeneration applications. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/42846

5. Nsiah, Barbara Akua. Fluid shear stress modulation of embryonic stem cell differentiation.

Degree: PhD, Mechanical Engineering, 2012, Georgia Tech

URL: http://hdl.handle.net/1853/47552

► Vascularization of tissue-engineered substitutes is imperative for successful implantation into sites of injury. Strategies to promote vascularization within tissue-engineered constructs have focused on incorporating endothelial… (more)

▼ Vascularization of tissue-engineered substitutes is imperative for successful implantation into sites of injury. Strategies to promote vascularization within tissue-engineered constructs have focused on incorporating endothelial or endothelial progenitor cells within the construct. However, since endothelial and endothelial progenitor cells are adult cell types and limited in number, acquiring quantities needed for regenerative medicine applications is not feasible. Pluriopotent stem cells have been explored as a cell source for tissue-engineered substitutes because of their inherent ability to differentiate into all somatic cell types, including endothelial cells (ECs). Current EC differentiation strategies require laborious and extensive culture periods, utilize large quantities of expensive growth factors and extracellular matrix, and generally yield heterogenous populations for which only a small percentage of the differentiated cells are ECs. In order to recapitulate in vivo embryonic stem cell (ESC) differentiation, 3D stem cell aggregates or embryoid bodies (EBs) have been employed in vitro. In the developing embryo, fluid shear stress, VEGF, and oxygen are instructive cues for endothelial differentiation and vasculogenesis. Thus, the objective of this work was to study the effects of fluid shear stress pre-conditioning of ESCs on EB endothelial differentiation and vasculogensis. The overall hypothesis is that exposing ESCs to fluid shear stress prior to EB differentiation will promote EB endothelial differentiation and vasculogenesis. Pre-conditioning ESCs with fluid shear stress modulated EB differentiation as well as endothelial cell-like cellular organization and EB morphogenesis. To further promote endothelial differentiation, ESCs pre-conditioned with shear were treated with VEGF. Exposing EBs formed from ESCs pre-conditioned with shear to low oxygen resulted in increased production of VEGF and formation of endothelial networks. The results of this work demonstrate the role that physical forces play in modulating stem cell fate and morphogenesis. Advisors/Committee Members: Nerem, Robert M. (Committee Chair), McDevitt, Todd C. (Committee Co-Chair), Gleason, Rudolph L. (Committee Member), Platt, Manu O. (Committee Member), Zamir, Evan A. (Committee Member).

Subjects/Keywords: Vasculogenesis; Morphogenesis; Differentiation; Fluid shear; Stem cells; Tissue engineering; Regenerative medicine; Cell differentiation; Endothelial cells

…Georgia Tech. This program has provided me with numerous mentors such as Dr. Gary May, Dr… …Rob have been constant supports while at Georgia Tech. My parents would call to check up on…

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APA (6^th Edition):

Nsiah, B. A. (2012). Fluid shear stress modulation of embryonic stem cell differentiation. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/47552

Chicago Manual of Style (16^th Edition):

Nsiah, Barbara Akua. “Fluid shear stress modulation of embryonic stem cell differentiation.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/47552.

MLA Handbook (7^th Edition):

Nsiah, Barbara Akua. “Fluid shear stress modulation of embryonic stem cell differentiation.” 2012. Web. 21 Apr 2021.

Vancouver:

Nsiah BA. Fluid shear stress modulation of embryonic stem cell differentiation. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/47552.

Council of Science Editors:

Nsiah BA. Fluid shear stress modulation of embryonic stem cell differentiation. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/47552

6. Holliday, Casey Jane. Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium.

Degree: PhD, Biomedical Engineering, 2012, Georgia Tech

URL: http://hdl.handle.net/1853/47517

► Aortic valve (AV) disease is a major cause of cardiovascular-linked deaths globally. In addition, AV disease is a strong risk factor for additional cardiovascular events;… (more)

▼ Aortic valve (AV) disease is a major cause of cardiovascular-linked deaths globally. In addition, AV disease is a strong risk factor for additional cardiovascular events; however, the mechanism by which it initiates and progresses is not well-understood. We hypothesize that low and oscillatory flow is present on the fibrosa side of the AV and stimulates ECs to differentially regulate microRNA (miRNA) and mRNAs and influence AV disease progression. This hypothesis was tested employing both in vitro and in vivo approaches, high throughput microarray and pathway analyses, as well as a variety of functional assays. First, we isolated and characterized side-dependent, human aortic valvular endothelial cells (HAVECs). We found that HAVECs express both endothelial cell markers (VE-Cadherin, vWF, and PECAM) as well as smooth muscle cell markers (SMA and basic calponin). Using microarray analysis on sheared, side-specific HAVECs, we identified side- and shear-induced changes in miRNA and mRNA expression profiles. More specifically, we identified over 1000 shear-responsive mRNAs which showed robust validation (93% of those tested). We then used Ingenuity Pathway Analysis to identify key miRNAs, including those with many relationships to other genes (for example, thrombospondin and I&B) and those that are members of over-represented pathways and processes (for example, sulfur metabolism). Furthermore, we validated five shear-sensitive miRNAs: miR-139-3p, miR-148a, miR-187, miR-192, and miR-486-5p and one side-dependent miRNA, miR-370. To prioritize these miRNAs, we performed in silico analysis to group these key miRNAs by cellular functions related to AV disease (including tissue remodeling, inflammation, and calcification). Next, to compare our in vitro HAVEC results in vivo, we developed a method to isolate endothelial-enriched, side-dependent total RNA and identify and validate side-dependent (fibrosa vs. ventricularis) miRNAs in porcine aortic valvular endothelium. From this analysis, we discovered and validated eight side-dependent miRNAs in porcine endothelial-enriched AV RNA, including one miRNA previously identified in vitro, miR-486-5p. Lastly, we determined the relationship between important miRNAs (specifically miR-187 and miR-486-5p) and AV disease by modulating levels of miRNAs and performing functional assays. Preliminary studies overexpressing miR-187 in HAVECs have shown a reduction in inflammatory state through monocyte adhesion (p<0.05). Further, miR-486-5p overexpression reveals an increase in migration (p<0.05) and a trend for a decrease in early apoptosis, linking miR-486-5p to tissue remodeling in the AV. Better understanding of AV biology and disease in terms of gene-regulation under different hemodynamic conditions will facilitate the design of a tissue-engineered valve and provide alternative treatment options. Advisors/Committee Members: Jo, Hanjoong (Committee Co-Chair), Nerem, Robert. M (Committee Co-Chair), Eskin, Suzanne (Committee Member), Taylor, W. Robert (Committee Member), Thourani, Vinod (Committee Member), Yoganathan, Ajit (Committee Member).

Subjects/Keywords: Aortic valve; Endothelium; MicroRNAs; Shear stress; Microarrays; MRNAs; Aortic valve Diseases; Aortic valve Stenosis; Messenger RNA; Vascular endothelium

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APA (6^th Edition):

Holliday, C. J. (2012). Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/47517

Chicago Manual of Style (16^th Edition):

Holliday, Casey Jane. “Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/47517.

MLA Handbook (7^th Edition):

Holliday, Casey Jane. “Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium.” 2012. Web. 21 Apr 2021.

Vancouver:

Holliday CJ. Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/47517.

Council of Science Editors:

Holliday CJ. Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/47517

7. Raykin, Julia. A theoretical and experimental model to predict biaxial failure of tissue engineered blood vessels.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2013, Georgia Tech

URL: http://hdl.handle.net/1853/50211

► The development of small diameter tissue engineered blood vessels (TEBVs) with low thrombogenicity, low immunogenicity, suitable mechanical properties, and a capacity to remodel to their… (more)

Subjects/Keywords: Tissue engineering; Vascular grafts; Blood vessel; Vessel failure; Volumetric growth; Damage mechanics; Biomedical engineering; Biomedical materials; Blood vessel prosthesis; Blood-vessels

…all of the friends that I have made during graduate career at Georgia Tech. It would be… …Karan were the first friends I made at Georgia Tech. I really appreciate their open-mindedness…

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APA (6^th Edition):

Raykin, J. (2013). A theoretical and experimental model to predict biaxial failure of tissue engineered blood vessels. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/50211

Chicago Manual of Style (16^th Edition):

Raykin, Julia. “A theoretical and experimental model to predict biaxial failure of tissue engineered blood vessels.” 2013. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/50211.

MLA Handbook (7^th Edition):

Raykin, Julia. “A theoretical and experimental model to predict biaxial failure of tissue engineered blood vessels.” 2013. Web. 21 Apr 2021.

Vancouver:

Raykin J. A theoretical and experimental model to predict biaxial failure of tissue engineered blood vessels. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/50211.

Council of Science Editors:

Raykin J. A theoretical and experimental model to predict biaxial failure of tissue engineered blood vessels. [Doctoral Dissertation]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/50211

8. Broiles, JoSette Leigh Briggs. The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype.

Degree: PhD, Mechanical Engineering, 2008, Georgia Tech

URL: http://hdl.handle.net/1853/22652

► An increase in coronary disease prevalence and mortality highlights the growing need for therapies to treat atherosclerotic vessels. While current bypass procedures utilize autologous vessels… (more)

Subjects/Keywords: Tissue engineering; Smooth muscle cells; Tropoelastin; Versican; Muscle cells; Tissue engineering; Blood vessel prosthesis; Elastin

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APA (6^th Edition):

Broiles, J. L. B. (2008). The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/22652

Chicago Manual of Style (16^th Edition):

Broiles, JoSette Leigh Briggs. “The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype.” 2008. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/22652.

MLA Handbook (7^th Edition):

Broiles, JoSette Leigh Briggs. “The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype.” 2008. Web. 21 Apr 2021.

Vancouver:

Broiles JLB. The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype. [Internet] [Doctoral dissertation]. Georgia Tech; 2008. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/22652.

Council of Science Editors:

Broiles JLB. The use of a tissue engineered media equivalent in the study of a novel smooth muscle cell phenotype. [Doctoral Dissertation]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/22652

Georgia Tech

9. Xing, Yun. Effects of Mechanical Forces on the Biological Properties of Porcine Aortic Valve Leaflets.

Degree: PhD, Bioengineering, 2005, Georgia Tech

URL: http://hdl.handle.net/1853/6828

► Cardiac valves are dynamic, sophisticated structures which interact closely with the surrounding hemodynamic environment. Altered mechanical stresses, including pressure, shear and bending stresses, are believed… (more)

▼ Cardiac valves are dynamic, sophisticated structures which interact closely with the surrounding hemodynamic environment. Altered mechanical stresses, including pressure, shear and bending stresses, are believed to cause changes in valve biology, but the cellular and molecular events involved in these processes are not well characterized. Therefore, the overall goal of this project is to determine the effects of pressure and shear stress on porcine aortic valve leaflets biology. Results from the pressure study showed that elevated constant pressure (140 and 170 mmHg) causes significant increases in collagen synthesis. The increases were 37.5% and 90% for 140 and 170 mmHg, respectively. No significant differences in DNA and sGAG synthesis were observed under constant pressure. In the cyclic pressure study, the effects of both pressure magnitude and pulse frequency were studied. With the frequency fixed at 1.167 Hz, collagen and sGAG synthesis increased proportionally with mean pressure level. At a fixed pressure level (80-120 mmHg), collagen and sGAG synthesis were slightly increased by 25% and 14% at 0.5 Hz, respectively. DNA synthesis was significantly increased by 72% at 2 Hz. An experiment combining high magnitude (150-190 mmHg) and high frequency (2 Hz) demonstrated significant increases in collagen and sGAG synthesis (collagen: 74%, sGAG: 56%), but no significant changes in cell proliferation. Shear levels ranging from 1 to 80 dyne/cm2 were studied. Scanning electron microscopy results indicated that 48 hrs exposure to shear stress did not alter the circumferential alignment of endothelial cells. Collagen synthesis was significantly enhanced at 9 and 25 dyne/cm2, but not different from static controls under other shear conditions. Leaflets denuded of the endothelium were exposed to identical shear stress and showed very different responses. Collagen synthesis was not affected at any shear levels, but sGAG content was increased at shear of 9, 25 and 40 dyne/cm2. Further studies showed that the increases in collagen synthesis under pressure or shear stress was concurrent with a decline in the expression and activities of cathepsins L and S. This converse relationship between collagen synthesis and cathepsin activity indicated that cathepsins might be involved in valvular ECM remodeling. Advisors/Committee Members: Yoganathan, Ajit (Committee Chair), Hilbert, Steve (Committee Member), Jo, Hanjoong (Committee Member), Nerem, Robert (Committee Member), Wick, Timothy (Committee Member).

Subjects/Keywords: Heart valves; Mechanical forces; Tissue engineering; Shear flow; Strains and stresses; Heart valves; Hemodynamics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Xing, Y. (2005). Effects of Mechanical Forces on the Biological Properties of Porcine Aortic Valve Leaflets. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/6828

Chicago Manual of Style (16^th Edition):

Xing, Yun. “Effects of Mechanical Forces on the Biological Properties of Porcine Aortic Valve Leaflets.” 2005. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/6828.

MLA Handbook (7^th Edition):

Xing, Yun. “Effects of Mechanical Forces on the Biological Properties of Porcine Aortic Valve Leaflets.” 2005. Web. 21 Apr 2021.

Vancouver:

Xing Y. Effects of Mechanical Forces on the Biological Properties of Porcine Aortic Valve Leaflets. [Internet] [Doctoral dissertation]. Georgia Tech; 2005. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/6828.

Council of Science Editors:

Xing Y. Effects of Mechanical Forces on the Biological Properties of Porcine Aortic Valve Leaflets. [Doctoral Dissertation]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/6828

Georgia Tech

10. Brown, Lola A. The Effects of Sickle Erythrocytes on Endothelial Permeability.

Degree: MS, Biomedical Engineering, 2005, Georgia Tech

URL: http://hdl.handle.net/1853/6960

► Sickle cell anemia is a hematological disorder that is caused by a single point mutation in the beta-globin chain of hemoglobin. It results in several… (more)

▼ Sickle cell anemia is a hematological disorder that is caused by a single point mutation in the beta-globin chain of hemoglobin. It results in several complications related to the small and large vessels in patients with the disease. Large vessel complications include cerebral infarcts, which are observed in children under ten years old. The mechanism behind this complication is not completely understood. It is the goal of this project to begin to understand the role sickle erythrocytes may play in causing endothelial dysfunction as a precursor to sickle related complications. The hypothesis of this work is that exposure of large vessel endothelium to sickle erythrocytes causes an increase in endothelial permeability through loosening of adherens junctions. In the first goal of this work, bovine aortic endothelial cells (BAECs) are grown on coverslips and exposed to sickle erythrocytes for 5 minutes and either immediately fixed or incubated in 30 minutes and then fixed. Immunofluorescent studies labeling VE cadherin show changes in VE cadherin dynamics, suggesting sickle erythrocytes may be involved in this observation. Next, BAECs were grown on transwell inserts and exposed to sickle erythrocytes for 5 minutes. The erythrocytes are washed off and the BAEC are incubated with 10,000 MW dextran conjugated to lucifer yellow or FITC-BSA or to determine BAEC permeability. When dextran is used as the test molecule, endothelial permeability did not show a significant change from baseline. However, when BSA is used as the test molecule, increases in endothelial permeability are observed. Explanations into the differences between the transport mechanisms of the two molecules are discussed. These experiments show changes in VE cadherin localization due to sickle erythrocyte exposure. This may cause increases in endothelial permeability and an experimental model and preliminary studies are performed. This study provides potential mechanisms to explain the changes in VE cadherin localization and provide suggestions for further studies to test the effect of sickle erythrocytes on endothelial permeability. This work provides a strong foundation for continuing studies on the effects of sickle erythrocytes on endothelial dysfunction within the confines of sickle related complications. Advisors/Committee Members: Wick, Timothy (Committee Chair), Barabino, Gilda (Committee Co-Chair), Eckman, James (Committee Member), Nerem, Robert (Committee Member).

Subjects/Keywords: Permeability coefficient; VE cadherin; Stroke; Endothelial cells; Sickle cell anemia

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APA (6^th Edition):

Brown, L. A. (2005). The Effects of Sickle Erythrocytes on Endothelial Permeability. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/6960

Chicago Manual of Style (16^th Edition):

Brown, Lola A. “The Effects of Sickle Erythrocytes on Endothelial Permeability.” 2005. Masters Thesis, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/6960.

MLA Handbook (7^th Edition):

Brown, Lola A. “The Effects of Sickle Erythrocytes on Endothelial Permeability.” 2005. Web. 21 Apr 2021.

Vancouver:

Brown LA. The Effects of Sickle Erythrocytes on Endothelial Permeability. [Internet] [Masters thesis]. Georgia Tech; 2005. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/6960.

Council of Science Editors:

Brown LA. The Effects of Sickle Erythrocytes on Endothelial Permeability. [Masters Thesis]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/6960

Georgia Tech

11. Ensley, Ann Elizabeth. Functional evaluation of circulating endothelial progenitor cells for vascular tissue engineering.

Degree: PhD, Biomedical Engineering, 2006, Georgia Tech

URL: http://hdl.handle.net/1853/10491

► One critical barrier to the success of vascular tissue engineering strategies is the need for appropriate endothelial cell sources. Adult stem and progenitor cells have… (more)

Subjects/Keywords: Cardiovascular

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APA (6^th Edition):

Ensley, A. E. (2006). Functional evaluation of circulating endothelial progenitor cells for vascular tissue engineering. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/10491

Chicago Manual of Style (16^th Edition):

Ensley, Ann Elizabeth. “Functional evaluation of circulating endothelial progenitor cells for vascular tissue engineering.” 2006. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/10491.

MLA Handbook (7^th Edition):

Ensley, Ann Elizabeth. “Functional evaluation of circulating endothelial progenitor cells for vascular tissue engineering.” 2006. Web. 21 Apr 2021.

Vancouver:

Ensley AE. Functional evaluation of circulating endothelial progenitor cells for vascular tissue engineering. [Internet] [Doctoral dissertation]. Georgia Tech; 2006. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/10491.

Council of Science Editors:

Ensley AE. Functional evaluation of circulating endothelial progenitor cells for vascular tissue engineering. [Doctoral Dissertation]. Georgia Tech; 2006. Available from: http://hdl.handle.net/1853/10491

Georgia Tech

12. Vanderploeg, Eric James. Mechanotransduction in Engineered Cartilaginous Tissues: In Vitro Oscillatory Tensile Loading.

Degree: PhD, Mechanical Engineering, 2006, Georgia Tech

URL: http://hdl.handle.net/1853/11483

► Disease and degeneration of articular cartilage and fibrocartilage tissues severely compromise the quality of life for millions of people. Although current surgical repair techniques can… (more)

▼ Disease and degeneration of articular cartilage and fibrocartilage tissues severely compromise the quality of life for millions of people. Although current surgical repair techniques can address symptoms in the short term, they do not adequately treat degenerative joint diseases such as osteoarthritis. Thus, novel tissue engineering strategies may be necessary to combat disease progression and repair or replace damaged tissue. Both articular cartilage and the meniscal fibrocartilage in the knee joint are subjected to a complex mechanical environment consisting of compressive, shear, and tensile forces. Therefore, engineered replacement tissues must be both mechanically and biologically competent to function after implantation. The goal of this work was to investigate the effects of oscillatory tensile loading on three dimensional engineered cartilaginous tissues in an effort to elucidate important aspects of chondrocyte and fibrochondrocyte mechanobiology. To investigate the metabolic responses of articular chondrocytes and meniscal fibrochondrocytes to oscillatory tensile loading, various protocols were used to identify stimulatory parameters. Several days of continuously applied tensile loading inhibited extracellular matrix metabolism, whereas short durations and intermittently applied loading could stimulate matrix production. Subpopulations of chondrocytes, separated based on their zonal origin within the tissue, differentially responded to tensile loading. Proteoglycan synthesis was enhanced in superficial zone cells, but the molecular structure of these molecules was not affected. In contrast, neither total proteoglycan nor protein synthesis levels of middle and deep zone chondrocytes were substantially affected by tensile loading; however, the sizes of these new matrix molecules were altered. Up to 14 days of intermittently applied oscillatory tensile loading induced modest increases in construct mechanical properties, but longer durations adversely affected these mechanical properties and increased degradative enzyme activity. These results provide insights into cartilage and fibrocartilage mechanobiology by elucidating cellular responses to tensile mechanical stimulation, which previously had not been widely explored for these tissues. Understanding the role that mechanical stimuli such as tension can play in the generation of engineered cartilaginous tissues will further the goal of developing successful treatment strategies for degenerative joint diseases. Advisors/Committee Members: Levenston, Marc (Committee Chair), Garcia, Andres (Committee Member), LaPlaca, Michelle (Committee Member), Nerem, Robert (Committee Member), Radhakrishna, Harish (Committee Member).

Subjects/Keywords: Tensile loading; Mechanical stimulation; Meniscus; Tissue engineering; Fibrocartilage; Cartilage; Tissue engineering; Loads (Mechanics); Biomechanics; Articular cartilage Mechanical properties

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APA (6^th Edition):

Vanderploeg, E. J. (2006). Mechanotransduction in Engineered Cartilaginous Tissues: In Vitro Oscillatory Tensile Loading. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/11483

Chicago Manual of Style (16^th Edition):

Vanderploeg, Eric James. “Mechanotransduction in Engineered Cartilaginous Tissues: In Vitro Oscillatory Tensile Loading.” 2006. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/11483.

MLA Handbook (7^th Edition):

Vanderploeg, Eric James. “Mechanotransduction in Engineered Cartilaginous Tissues: In Vitro Oscillatory Tensile Loading.” 2006. Web. 21 Apr 2021.

Vancouver:

Vanderploeg EJ. Mechanotransduction in Engineered Cartilaginous Tissues: In Vitro Oscillatory Tensile Loading. [Internet] [Doctoral dissertation]. Georgia Tech; 2006. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/11483.

Council of Science Editors:

Vanderploeg EJ. Mechanotransduction in Engineered Cartilaginous Tissues: In Vitro Oscillatory Tensile Loading. [Doctoral Dissertation]. Georgia Tech; 2006. Available from: http://hdl.handle.net/1853/11483

Georgia Tech

13. Butcher, Jonathan Talbot. The Effects of Steady Laminar Shear Stress on Aortic Valve Cell Biology.

Degree: PhD, Mechanical Engineering, 2004, Georgia Tech

URL: http://hdl.handle.net/1853/4824

► Aortic valve disease (AVD) affects millions of people of all ages around the world. Current treatment for AVD consists of valvular replacement with a non-living… (more)

▼ Aortic valve disease (AVD) affects millions of people of all ages around the world. Current treatment for AVD consists of valvular replacement with a non-living prosthetic valve, which is incapable of growth, self-repair, or remodeling. While tissue engineering has great promise to develop a living heart valve alternative, success in animal models has been limited. This may be attributed to the fact that understanding of valvular cell biology has not kept pace with advances in biomaterial development. Aortic valve leaflets are exposed to a complex and dynamic mechanical environment unlike any in the vasculature, and it is likely that native endothelial and interstitial cells respond to mechanical forces differently from other vascular cells. The objective of this thesis was to compare valvular cell phenotype to vascular cell phenotype, and assess the influence of steady shear stress on valvular cell biology. This thesis demonstrates that valvular endothelial cells respond differently to shear than vascular endothelial cells, by aligning perpendicular to the direction of steady shear stress, and by the differential regulation of hundreds of genes in both static and fluid flow environments. Valvular interstitial cells expressed a combination of contractile and synthetic phenotypes not mimicked by vascular smooth muscle cells. Two three-dimensional leaflet models were developed to assess cellular interactions and the influences of steady laminar shear stress. Valvular co-culture models exhibited a physiological response profile, while interstitial cell-only constructs behaved more pathologically. Steady shear stress enhanced physiological functions of valvular co-cultures, but increased pathological response of interstitial cell-only constructs. These results showed that valvular cells, whether cultured separately or together, behaved distinctly different from vascular cells. It was also determined that shear stress alone cannot induce tissue remodeling to more resemble native valve leaflets. The leaflet models developed in this thesis can be used in future experiments to explore valvular cell biology, assess the progression of certain forms AVD, and develop targeted diagnostic and therapeutic strategies to hopefully eliminate the need for valvular replacement entirely. Advisors/Committee Members: Nerem, Robert M (Committee Chair), Garcia, Andres (Committee Member), Hilbert, Stephen L (Committee Member), Jo, Hanjoong (Committee Member), Yoganathan, Ajit P (Committee Member).

Subjects/Keywords: Microarray; Interstitial cells; Aortic valve; Shear stress; Endothelial cells

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APA (6^th Edition):

Butcher, J. T. (2004). The Effects of Steady Laminar Shear Stress on Aortic Valve Cell Biology. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/4824

Chicago Manual of Style (16^th Edition):

Butcher, Jonathan Talbot. “The Effects of Steady Laminar Shear Stress on Aortic Valve Cell Biology.” 2004. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/4824.

MLA Handbook (7^th Edition):

Butcher, Jonathan Talbot. “The Effects of Steady Laminar Shear Stress on Aortic Valve Cell Biology.” 2004. Web. 21 Apr 2021.

Vancouver:

Butcher JT. The Effects of Steady Laminar Shear Stress on Aortic Valve Cell Biology. [Internet] [Doctoral dissertation]. Georgia Tech; 2004. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/4824.

Council of Science Editors:

Butcher JT. The Effects of Steady Laminar Shear Stress on Aortic Valve Cell Biology. [Doctoral Dissertation]. Georgia Tech; 2004. Available from: http://hdl.handle.net/1853/4824

Georgia Tech

14. Ankeny, Randall Francis. The role of bone morphogenic proteins in human aortic valvular endothelial cells.

Degree: PhD, Biomedical Engineering, 2010, Georgia Tech

URL: http://hdl.handle.net/1853/39571

► In the United States alone, there are nearly 49,000 aortic valvular repairs or replacements each year, and this number is expected to rise. Unlike atherosclerosis,… (more)

▼ In the United States alone, there are nearly 49,000 aortic valvular repairs or replacements each year, and this number is expected to rise. Unlike atherosclerosis, the molecular mechanisms contributing to this side-dependent disease development are limited, which contributes to the lack of therapeutic treatments. Once clinically manifested, options for treatment are limited to valvular replacement or repair. Therefore understanding the mechanobiology and cellular responses in aortic valves may provide important information for disease development and possible biomarkers or therapeutic treatments. Aortic valve disease occurs on one side of the valvular leaflet. The fibrosa side, which faces the aorta, is prone to disease development, while the ventricularis remains relatively unaffected. The hemodynamics is hypothesized to play a role in side dependent disease formation. The fibrosa endothelium is exposed to oscillatory flow while the ventricularis endothelium is exposed to a pulsatile unidirectional flow. Previous work by our group has shown that bone morphogenic protein-4 is a mechanosensitve inflammatory cytokine in the vasculature. In the following study, we proposed that mechanosensitive bone morphogenic proteins play a role in side specific aortic valve disease. Recently, the bone morphogenic proteins (BMPs) have been found in calcified human aortic valves. Furthermore, BMP-4 in vascular endothelial cells is increased by oscillatory shear stress. However, the role of the BMPs in aortic valve endothelial cells and their contribution to aortic valve calcification remains unstudied. Therefore, the overall objective of this dissertation was to investigate how disease and hemodynamics affects the BMP pathway and inflammation in human aortic valvular endothelial cells. By understanding how the bone morphogenic proteins are regulated and what roles they play in aortic valve disease, we will have better insight into endothelial cell regulation and contribution in aortic valve pathology. The central hypothesis of this project was that oscillatory flow conditions on the fibrosa side of the aortic valve stimulate endothelial cells to produce BMP-4, which then activates an inflammatory response leading to accumulation of inflammatory cells, calcification, and ultimately valve impairment. This hypothesis was tested through three specific aims using calcified human aortic valves, non-calcified human aortic valves, and side-specific human aortic valve endothelial cells. We first worked to establish the importance of the BMPs in the aortic valvular endothelium by looking at two populations of aortic valves: 1) calcified human aortic valves were obtained from patients undergoing valve replacement, and 2) non-calcified valves were obtained from recipient hearts of patients undergoing heart transplantation. Using immunohistochemical techniques, we examined the BMPs, BMP antagonists, and SMADs. Surprisingly, we identified that the ventricularis endothelium had higher BMP expression in both calcified and… Advisors/Committee Members: Jo, Hanjoong (Committee Chair), Nerem, Robert M. (Committee Co-Chair), Oshinski, John (Committee Member), Thourani, Vinod (Committee Member), Yoganathan, Ajit P. (Committee Member).

Subjects/Keywords: Calcification; Aortic valve; Bone morphogenic proteins; Endothelial cell; Aortic valve Surgery; Biomechanics; Hemodynamics; Vascular endothelium; Bone morphogenetic proteins

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APA (6^th Edition):

Ankeny, R. F. (2010). The role of bone morphogenic proteins in human aortic valvular endothelial cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/39571

Chicago Manual of Style (16^th Edition):

Ankeny, Randall Francis. “The role of bone morphogenic proteins in human aortic valvular endothelial cells.” 2010. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/39571.

MLA Handbook (7^th Edition):

Ankeny, Randall Francis. “The role of bone morphogenic proteins in human aortic valvular endothelial cells.” 2010. Web. 21 Apr 2021.

Vancouver:

Ankeny RF. The role of bone morphogenic proteins in human aortic valvular endothelial cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2010. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/39571.

Council of Science Editors:

Ankeny RF. The role of bone morphogenic proteins in human aortic valvular endothelial cells. [Doctoral Dissertation]. Georgia Tech; 2010. Available from: http://hdl.handle.net/1853/39571

Georgia Tech

15. Johnson, Tiffany Lynn. Endothelial Cell Function Using a Tissue Engineered Blood Vessel Model: A Case Study of Cell-Cell Communication.

Degree: PhD, Biomedical Engineering, 2006, Georgia Tech

URL: http://hdl.handle.net/1853/10489

► Atherosclerosis is an inflammatory disease which develops focally in regions of the vasculature where there is dysfunction of endothelial cells modulated in part by shear… (more)

▼ Atherosclerosis is an inflammatory disease which develops focally in regions of the vasculature where there is dysfunction of endothelial cells modulated in part by shear stress from flowing blood. To address the clinical crisis of atherosclerosis, tissue engineering has focused on development of a living blood vessel substitute for use as a vascular graft in bypass surgery. Despite substantial progress in understanding the biological basis and developing clinical treatments for cardiovascular disease, critical challenges remain. As a novel strategy to improve understanding of basic human vascular biology and develop superior tissue engineered grafts, this dissertation combines the scientific and clinical approaches by using a tissue engineered blood vessel as a more physiologic in vitro model to study endothelial cell biology. Through the use of transcriptional profiling, results demonstrate significant changes in endothelial cell gene expression using the tissue engineered blood vessel model. Furthermore, the presence of a more physiologic substrate alters the cellular response to shear stress which is a critical mediator of vascular pathology. A case study of endothelial cell function in this system focuses on cell-cell communication through gap junctions. Endothelial cell connexins which form gap junctions are shown to be differentially regulated by substrate and shear stress. Moreover, gap junction communication between endothelial cells is modulated by the mechanical environment. Studies using RNA interference to knockdown expression of individual connexin isotypes demonstrate integrated regulation of connexins yet unique roles in endothelial cell function. Collectively, results exemplify the sensitivity of endothelial cell phenotype to substrate and shear stress and underline the importance of using more physiologic models in the study of basic cell biology. Advisors/Committee Members: Nerem, Robert (Committee Chair), Galis, Zorina (Committee Member), Jo, Hanjoong (Committee Member), McIntire, Larry (Committee Member), Pollman, Matthew (Committee Member), Taylor, W Robert (Committee Member).

Subjects/Keywords: Gap junction; Connexin; Tissue engineering; Endothelial cells; Shear stress; Tissue engineering; Vascular endothelium; Atherosclerosis; Blood vessel prosthesis; Connexins; Gap junctions (Cell biology)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Johnson, T. L. (2006). Endothelial Cell Function Using a Tissue Engineered Blood Vessel Model: A Case Study of Cell-Cell Communication. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/10489

Chicago Manual of Style (16^th Edition):

Johnson, Tiffany Lynn. “Endothelial Cell Function Using a Tissue Engineered Blood Vessel Model: A Case Study of Cell-Cell Communication.” 2006. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/10489.

MLA Handbook (7^th Edition):

Johnson, Tiffany Lynn. “Endothelial Cell Function Using a Tissue Engineered Blood Vessel Model: A Case Study of Cell-Cell Communication.” 2006. Web. 21 Apr 2021.

Vancouver:

Johnson TL. Endothelial Cell Function Using a Tissue Engineered Blood Vessel Model: A Case Study of Cell-Cell Communication. [Internet] [Doctoral dissertation]. Georgia Tech; 2006. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/10489.

Council of Science Editors:

Johnson TL. Endothelial Cell Function Using a Tissue Engineered Blood Vessel Model: A Case Study of Cell-Cell Communication. [Doctoral Dissertation]. Georgia Tech; 2006. Available from: http://hdl.handle.net/1853/10489

Georgia Tech

16. Platt, Manu Omar. Role of Shear Stress in the Differential Regulation of Endothelial Cathepsins and Cystatin C.

Degree: PhD, Biomedical Engineering, 2006, Georgia Tech

URL: http://hdl.handle.net/1853/11635

► The importance of shear stress in vascular biology and pathophysiology has been highlighted by the focal development patterns of atherosclerosis, abdominal aortic aneurysms, and heart… (more)

▼ The importance of shear stress in vascular biology and pathophysiology has been highlighted by the focal development patterns of atherosclerosis, abdominal aortic aneurysms, and heart valve disease in regions exposed to disturbed flow leading to low or oscillatory shear stress at the wall of the blood vessel or the surface of the valve leaflet. The novel and significant finding of this study is that mouse aortic endothelial cell exposure to pro-atherogenic oscillatory shear stress (OS) (+/- 5 dynes/cm2) increased their production of cathepsins, the family of lysosomal cysteine proteases that are potent elastases and collagenases leading to protease degradation and remodeling of the extracellular matrix structural components. Conversely, atheroprotective unidirectional laminar shear stress (LS) (15 dynes/cm2) decreased elastase and gelatinase activities of endothelial cells through a shear stress mediated reduction in cathepsins K, L, and S activity. Their endogenous inhibitor, cystatin C, was found to be inversely regulated by shear stress; LS increased its secretion by endothelial cells while OS decreased it. Binding of free cystatin C in the conditioned media to carboxymethylated papain coated agarose beads led to an increase in cathepsin activity since the available cathepsin was not inhibited. To verify these findings in human samples, immunohistochemical analysis of cystatin C and cathepsin K was performed on human coronary arteries. Cathepsin K stained strongly in the endothelial layer of vessels with degraded internal elastic lamina while cystatin C staining intensity was strongest overlying minimally diseased vessels. Additional roles for cathepsins K, L, and S were found in endothelial cell alignment in response to unidirectional laminar shear stress, endothelial cell migration, and programmed cell death. We conclude that there is an inverse regulation of cathepsins and cystatin C in endothelial cells by LS and OS and identify the cathepsin family of proteases as potential targets for therapeutic intervention of cardiovascular disease development at sites of disturbed flow. Advisors/Committee Members: Jo, Hanjoong (Committee Chair), Galis, Zorina (Committee Member), Nerem, Robert (Committee Member), Shi, Guo-Ping (Committee Member), Taylor, W Robert (Committee Member).

Subjects/Keywords: Shear stress; Cathepsins; Atherosclerosis; Endothelial cells; Vascular endothelium; Endothelial seeding; Atherosclerosis

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APA (6^th Edition):

Platt, M. O. (2006). Role of Shear Stress in the Differential Regulation of Endothelial Cathepsins and Cystatin C. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/11635

Chicago Manual of Style (16^th Edition):

Platt, Manu Omar. “Role of Shear Stress in the Differential Regulation of Endothelial Cathepsins and Cystatin C.” 2006. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/11635.

MLA Handbook (7^th Edition):

Platt, Manu Omar. “Role of Shear Stress in the Differential Regulation of Endothelial Cathepsins and Cystatin C.” 2006. Web. 21 Apr 2021.

Vancouver:

Platt MO. Role of Shear Stress in the Differential Regulation of Endothelial Cathepsins and Cystatin C. [Internet] [Doctoral dissertation]. Georgia Tech; 2006. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/11635.

Council of Science Editors:

Platt MO. Role of Shear Stress in the Differential Regulation of Endothelial Cathepsins and Cystatin C. [Doctoral Dissertation]. Georgia Tech; 2006. Available from: http://hdl.handle.net/1853/11635

Georgia Tech

17. Higgins, Adam Zachary. Intracellular ice formation in tissue constructs and the effects of mass transport across the cell membrane.

Degree: PhD, Biomedical Engineering, 2007, Georgia Tech

URL: http://hdl.handle.net/1853/28166

► Long-term storage of tissue by cryopreservation is necessary for the efficient mass production of tissue engineered products, and for reducing the urgency and cost of… (more)

▼ Long-term storage of tissue by cryopreservation is necessary for the efficient mass production of tissue engineered products, and for reducing the urgency and cost of organ transplantation procedures. The goal of this work was to investigate the physical processes thought result in damage during tissue cryopreservation towards development of tissue cryopreservation strategies. Although mathematical models of cell dehydration and intracellular ice formation (IIF) have been successfully used to optimize cryopreservation procedures for cell suspensions, it is not currently possible to use this approach with tissue because of the lack of tissue-specific permeability parameters for predicting cell dehydration during tissue freezing, and because of the increased complexity of the IIF process in tissue. We have measured the membrane permeability properties of tissue comprising a cell monolayer using a fluorescence quenching technique, and compared the results to the corresponding cell suspensions, revealing significant differences in the membrane transport kinetics between monolayers and suspensions. These data enabled the prediction cell dehydration during freezing of cell monolayers. Whereas the mechanisms of IIF are relatively well understood in cell suspensions, tissue is susceptible to new IIF mechanisms. In particular, cell-cell interactions have been shown to increase the IIF probability by enabling the propagation of ice between neighboring cells. We investigated the effect of cell-cell interactions on IIF using genetically modified cells expressing different levels of intercellular junction proteins. A new IIF mechanism was observed in these cells associated with penetration of extracellular ice into the cell-cell interface, and the incidence of this IIF mechanism was reduced in cells expressing the tight junction protein occludin. In addition, we investigated the effect of the cytoplasm supercooling and viscosity on the kinetics of IIF in tissue. We found that increasing the viscosity or decreasing the supercooling significantly decreased the kinetics of IIF, suggesting that IIF protocols for tissue can be optimized by modulating the cytoplasm supercooling and viscosity. Together, these data represent an important step towards developing cryopreservation strategies for tissue. Advisors/Committee Members: Karlsson, Jens (Committee Chair), Nerem, Robert (Committee Co-Chair), Meda, Paolo (Committee Member), Prausnitz, Mark (Committee Member), Sands, Jeff (Committee Member), Zhu, Cheng (Committee Member).

Subjects/Keywords: Cryopreservation; Permeability; Cryopreservation of organs, tissues, etc; Tissue engineering; Dehydration (Physiology); Ice crystals Growth

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APA (6^th Edition):

Higgins, A. Z. (2007). Intracellular ice formation in tissue constructs and the effects of mass transport across the cell membrane. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/28166

Chicago Manual of Style (16^th Edition):

Higgins, Adam Zachary. “Intracellular ice formation in tissue constructs and the effects of mass transport across the cell membrane.” 2007. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/28166.

MLA Handbook (7^th Edition):

Higgins, Adam Zachary. “Intracellular ice formation in tissue constructs and the effects of mass transport across the cell membrane.” 2007. Web. 21 Apr 2021.

Vancouver:

Higgins AZ. Intracellular ice formation in tissue constructs and the effects of mass transport across the cell membrane. [Internet] [Doctoral dissertation]. Georgia Tech; 2007. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/28166.

Council of Science Editors:

Higgins AZ. Intracellular ice formation in tissue constructs and the effects of mass transport across the cell membrane. [Doctoral Dissertation]. Georgia Tech; 2007. Available from: http://hdl.handle.net/1853/28166

Georgia Tech

18. Schutte, Stacey C. A study of strength and vasoactivity in a tissue engineered vascular media.

Degree: PhD, Mechanical Engineering, 2009, Georgia Tech

URL: http://hdl.handle.net/1853/28241

► To be successful a tissue engineered small diameter blood vessel must be non-immunogenic, non-thrombogenic, have mechanical properties similar to native vessel and be vasoactive. The… (more)

▼ To be successful a tissue engineered small diameter blood vessel must be non-immunogenic, non-thrombogenic, have mechanical properties similar to native vessel and be vasoactive. The vascular media is responsible for the mechanical properties and the vasoactivity of the vessel. The collagen hydrogel approach has been long used and has many advantages, but has not yet achieved the mechanical integrity needed for implantation. No collagen-based tissue engineered vascular media has been shown to be vasoactive using culture techniques required to achieve the cell numbers needed to make a vascular graft. To study collagen synthesis, two model systems were used. Cells were seeded on top of an adsorbed collagen I or fibrin layer. Alternatively the cells were encapsulated in a collagen or fibrin hydrogel. Collagen I, decorin and biglycan synthesis was affected by both matrix type and presentation. After two weeks in culture the smooth muscle cells produce more type I collagen in the collagen based hydrogels then in the fibrin hydrogels and was used for further studies. The collagen based tissue engineered vascular media produced a consistent vasoactive response between two and eight weeks of culture. The smooth muscle cells have functional endothelin, kinin, adrenergic, serotonergic and purinergic receptors. The application of cyclic strain improves both the tissue strength and the contractile response. Use of transforming growth factor-β improved tissue strength, but reduced the contractile response. Transforming growth factor- β actually promoted a more contractile cell phenotype, but a stronger contractile force was required to overcome the thick compact collagen hydrogel and elicit a measurable contraction. This work adds to what is known about collagen-based tissue engineered vascular medias by identifying means of improving not only strength but vasoactivity. The trade-offs found between these two important characteristics are relevant to all tissue engineered medias. Advisors/Committee Members: Nerem, Robert M. (Committee Chair), Gleason, Rudolf L. (Committee Member), Taylor, W. Robert (Committee Member), Vito, Raymond P. (Committee Member), Wang, Yadong (Committee Member).

Subjects/Keywords: Cardiovascular; Tissue engineering; Regenerative medicine; Vascular grafts; Blood-vessels; Blood vessel prosthesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schutte, S. C. (2009). A study of strength and vasoactivity in a tissue engineered vascular media. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/28241

Chicago Manual of Style (16^th Edition):

Schutte, Stacey C. “A study of strength and vasoactivity in a tissue engineered vascular media.” 2009. Doctoral Dissertation, Georgia Tech. Accessed April 21, 2021. http://hdl.handle.net/1853/28241.

MLA Handbook (7^th Edition):

Schutte, Stacey C. “A study of strength and vasoactivity in a tissue engineered vascular media.” 2009. Web. 21 Apr 2021.

Vancouver:

Schutte SC. A study of strength and vasoactivity in a tissue engineered vascular media. [Internet] [Doctoral dissertation]. Georgia Tech; 2009. [cited 2021 Apr 21]. Available from: http://hdl.handle.net/1853/28241.

Council of Science Editors:

Schutte SC. A study of strength and vasoactivity in a tissue engineered vascular media. [Doctoral Dissertation]. Georgia Tech; 2009. Available from: http://hdl.handle.net/1853/28241

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Open Access Theses and Dissertations