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You searched for +publisher:"University of North Carolina" +contributor:("Deb, Arjun"). Showing records 1 – 2 of 2 total matches.

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University of North Carolina

1. Ubil, Eric Scott. p53 mediated mesenchymal-to-endothelial transition is a novel mechanism of vasculogenesis after ischemic cardiac injury.

Degree: Biology, 2013, University of North Carolina

The mammalian heart displays limited regenerative capacity after acute ischemic injury and heals primarily through fibrosis. Recent therapeutic research has focused on increasing vasculature at the site of injury as a means of preserving remaining myocardium and improving cardiac function after injury. Other research has focused on the ability to reprogram cardiac fibroblasts using exogenous transcription factors to achieve a similar goal. However, the ability of cardiac fibroblasts to adopt alternate cellular fates in the absence of exogenous factors is unclear. Here, we demonstrate that a subset of cardiac fibroblasts adopts the physiological and anatomical characteristics of native endothelial cells after ischemic cardiac injury in the absence of any added factors. Using mice harboring genetically labeled fibroblasts (Col1a2-CreERT:R26RtdTomato), we show that approximately 30% of labeled cardiac fibroblasts in the injury border zone express endothelial markers such as VE-cadherin, eNOS, Occludin, and Claudin 5. Fibroblast derived endothelial cells comprised 25+/-2% of total luminal endothelial cells at the border zone 3 days after injury. To better understand fibroblast-endothelial transition we subjected cardiac fibroblasts to cellular stress (serum starvation) and found that they formed endothelium-like structures on Matrigel and up-regulated endothelial specific genes (e.g. VE-cadherin, Flk1, Flt1) 6-20 fold. We show that transition of fibroblasts to endothelial-like cells ex vivo is p53 dependent. Pharmacological inhibition of p53 using Pifithrin-α or genetic deletion in fibroblasts (Col1a2-CreERT:p53fl/fl) led to a 94% mean decrease in Matrigel tube formation and 90% reduction in endothelial gene expression. Moreover, using semi-quantitative immunofluorescent staining, we observed that p53 levels in cardiac fibroblasts were more than 6 fold higher at the injury border zone. Injection of a p53 activator, RITA, after injury doubled p53 levels in cardiac fibroblasts and increased the degree of mesenchymal-to-endothelial transition (MEndoT) by 43%. Enhanced MEndoT was also associated with decreased collagen deposition and improved heart function 7 days post injury. In summary, we show that cardiac fibroblasts adopt endothelial cell like fates after cardiac injury and contribute to the neovascularization of the injured region. Manipulation of MEndoT could represent a novel therapeutic strategy to increase post infarct angiogenesis and enhance function in the injured heart. Advisors/Committee Members: Ubil, Eric Scott, Deb, Arjun.

Subjects/Keywords: College of Arts and Sciences; Department of Biology

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

APA (6th Edition):

Ubil, E. S. (2013). p53 mediated mesenchymal-to-endothelial transition is a novel mechanism of vasculogenesis after ischemic cardiac injury. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:be21233a-1c94-430d-bc40-3ad7d687097e

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Ubil, Eric Scott. “p53 mediated mesenchymal-to-endothelial transition is a novel mechanism of vasculogenesis after ischemic cardiac injury.” 2013. Thesis, University of North Carolina. Accessed October 27, 2020. https://cdr.lib.unc.edu/record/uuid:be21233a-1c94-430d-bc40-3ad7d687097e.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Ubil, Eric Scott. “p53 mediated mesenchymal-to-endothelial transition is a novel mechanism of vasculogenesis after ischemic cardiac injury.” 2013. Web. 27 Oct 2020.

Vancouver:

Ubil ES. p53 mediated mesenchymal-to-endothelial transition is a novel mechanism of vasculogenesis after ischemic cardiac injury. [Internet] [Thesis]. University of North Carolina; 2013. [cited 2020 Oct 27]. Available from: https://cdr.lib.unc.edu/record/uuid:be21233a-1c94-430d-bc40-3ad7d687097e.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ubil ES. p53 mediated mesenchymal-to-endothelial transition is a novel mechanism of vasculogenesis after ischemic cardiac injury. [Thesis]. University of North Carolina; 2013. Available from: https://cdr.lib.unc.edu/record/uuid:be21233a-1c94-430d-bc40-3ad7d687097e

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of North Carolina

2. Wetzel-Strong, Sarah. Effect of adrenomedullin over-expression in the cardiovascular system during development and disease.

Degree: Cell Biology and Physiology, 2015, University of North Carolina

Since the discovery of adrenomedullin (Adm - gene; AM - protein) in 1993, many roles for this widely expressed peptide have been described in the cardiovascular system. Numerous studies have determined that circulating levels of AM in human blood are elevated during many disease conditions, leading to questions about the feasibility of using this peptide as a biomarker of disease severity, as well as inquiries into the function of elevated AM in these contexts. In order to evaluate the effect of elevated AM during disease, gene-targeting techniques were used to generate mice that constitutively over-express Adm, abbreviated as Admhi/hi. The initial phenotypical analysis of this line revealed that Admhi/hi mice have enlarged hearts due to hyperplasia during development. Through genetic approaches, we determined that Adm over-expression primarily in the epicardium promotes this cardiac hyperplasia. Analysis of Adm expression levels between male and female Admhi/hi animals led to the unexpected finding that female Admhi/hi mice express Adm at levels 60-times greater than wildtype controls in the heart; whereas Admhi/hi males over-express Adm by 3-fold in the heart. Previous studies have demonstrated that Adm expression can be induced by estrogen; however, the potential for estrogen-induced negative regulation of Adm had not been explored. We found that many estrogen-induced microRNAs target the 3'UTR of Adm, including the novel microRNA, miR-879, to balance Adm expression in the female heart. Finally, many groups have demonstrated that AM provides protection to the heart during cardiovascular disease. Nonetheless, whether the physiological elevation of AM during human disease affects disease progression remains unknown. We asked whether constitutive over-expression of AM in the context of chronic hypertension provided any benefit by crossing the renin transgenic mouse model of hypertension to the Admhi/hi line. From this study, we found that Adm over-expression did not alter the degree of hypertrophy or fibrosis in the heart. However, the results from this study are inconclusive, as the renin transgenic mice with wildtype levels of Adm did not exhibit the cardiac fibrosis previously reported, indicating that the mixed genetic background of our experimental animals alters cardiovascular pathology independent of Adm status. Advisors/Committee Members: Wetzel-Strong, Sarah, Caron, Kathleen, Sealock, Robert, Deb, Arjun, Lund, Pauline Kay, Taylor, Joan.

Subjects/Keywords: Physiology; School of Medicine; Department of Cell Biology and Physiology

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th Edition):

Wetzel-Strong, S. (2015). Effect of adrenomedullin over-expression in the cardiovascular system during development and disease. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:a0e5c581-09be-45c2-9181-f3dd435e726d

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Wetzel-Strong, Sarah. “Effect of adrenomedullin over-expression in the cardiovascular system during development and disease.” 2015. Thesis, University of North Carolina. Accessed October 27, 2020. https://cdr.lib.unc.edu/record/uuid:a0e5c581-09be-45c2-9181-f3dd435e726d.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Wetzel-Strong, Sarah. “Effect of adrenomedullin over-expression in the cardiovascular system during development and disease.” 2015. Web. 27 Oct 2020.

Vancouver:

Wetzel-Strong S. Effect of adrenomedullin over-expression in the cardiovascular system during development and disease. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2020 Oct 27]. Available from: https://cdr.lib.unc.edu/record/uuid:a0e5c581-09be-45c2-9181-f3dd435e726d.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wetzel-Strong S. Effect of adrenomedullin over-expression in the cardiovascular system during development and disease. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:a0e5c581-09be-45c2-9181-f3dd435e726d

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.