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You searched for +publisher:"Temple University" +contributor:("Kruger, Warren D.;"). Showing records 1 – 2 of 2 total matches.

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Temple University

1. Fang, Pu. HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL.

Degree: PhD, 2012, Temple University

Pharmacology

Homocysteine (Hcy) is a thiol amino acid formed upon methionine de - methylation. A number of studies have revealed an association between hyperhomocysteinemia (HHcy), in which plasma Hcy levels exceed 15 µM, and diabetic atherosclerosis [1]. Despite these associations, the mechanisms underlying HHcy - associated diabetic atherosclerosis have not been clearly defined. This study assessed the effect of HHcy on diabetic atherosclerosis and its underlying mechanisms. We established a mouse model with a combination of three metabolic disorders, including HHcy (to mimic human HHcy), hyperglycemic (to mimic type 1 diabetes) and dyslipidemia (to exacerbate ApoE-/- mouse's susceptibility to atherosclerosis). In this mouse model, severe HHcy was developed due to mouse Cbs deficiency (mean plasma Hcy 182 µM) in a noval HHcy mouse model (Tg-hCBS Cbs ApoE-/-) generated by our collaborator [2]. Hyperglycemia was developed by 50 mg/kg streptozotocin (STZ) consecutive injection for 5 days (mean blood glucose 397 mg / dL). Dyslipedimia was introduced by high fat (HF, 21.0 % by weight) diet to accelerate aortic lesion formation in the Tg-hCBS Cbs ApoE-/- mice. An inducible human CBS (hCBS) transgene (Tg) was introduced to circumvent the neonatal lethality due to the mouse Cbs deficiency (Tg-hCBS Cbs-/- ApoE-/- mice). A zinc supplement in water could induce hCBS transgene expression and reverse Hcy level (reduced plasma Hcy from 182 µM to 5 µM, p < 0.001). Severe HHcy aggravated metabolic abnormalities, including increased urine secretion (from 8.35 ± 6.81 g/d/mouse in hyperglycemia only mice to 21.14 ± 5.95 g / d / mouse in hyperglycemic HHcy mice, p=0.042), increased water consumption (from 27.28 ± 9.46 g / d / mouse to 44.20 ± 4.66 g / d / mouse, p = 0.026), increased blood glucose level (from 443.20 ± 107.82 mg / dL to 614.27 ± 199.36 mg/dL, p = 0.031), increased heart weight (from 0.08 ± 0.02 g / cm to 0.11 ± 0.03 g / cm, p = 0.031) (data not shown) and decreased body weight (from -0.05 ± 0.92 g / 2 weeks / mouse to -1.78 ± 2.38 g / 2 weeks / mouse, p = 0.017). Hcy-lowering by zinc water reversed HHcy - induced hyperglycemia (from 614.27 ± 199.36 mg / dL to 440.20 ± 134.37 mg / dL, p = 0.032), increased urine secretion (from 21.14 ± 5.95 g / d / mouse to 0.90 ± 1.24 g / d / mouse, p = 0.042), and increased water consumption (from 44.20 ± 4.66 g / d / mouse to 6.08 ± 1.84 g / d / mouse, p = 0.008) in hyperglycemic mice. Increased atherosclerotic lesions were also found in the aortic roots of hyperglycemic HHcy mice (from 30.38 ± 14.34 % of the lumen area to 48.18 ± 12.07 %, p = 0.040). Increased accumulation of monocytes (MCs) and inflammatory MCs were found in atherosclerotic lesions of hyperglycemic HHcy mice. By sequential double immune - fluorescence staining with monoclonal antibodies (mAbs) anti MOMA - 2 (MC / macrophage [MØ] marker) and anti - Ly6C (inflammatory MC marker), we found that hyperglycemic HHcy mice had the largest area and percentage of MC / MØ (MOMA - 2+), and the largest area and percentage…

Advisors/Committee Members: Wang, Hong;, Yang, Xiao-Feng, Merali, Salim, Autieri, Michael V., Ashby, Barrie, Kruger, Warren D.;.

Subjects/Keywords: Pharmacology

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APA (6th Edition):

Fang, P. (2012). HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,223888

Chicago Manual of Style (16th Edition):

Fang, Pu. “HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL.” 2012. Doctoral Dissertation, Temple University. Accessed October 22, 2020. http://digital.library.temple.edu/u?/p245801coll10,223888.

MLA Handbook (7th Edition):

Fang, Pu. “HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL.” 2012. Web. 22 Oct 2020.

Vancouver:

Fang P. HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL. [Internet] [Doctoral dissertation]. Temple University; 2012. [cited 2020 Oct 22]. Available from: http://digital.library.temple.edu/u?/p245801coll10,223888.

Council of Science Editors:

Fang P. HYPERHOMOCYSTEINEMIA ACCELERATES ATHEROSCLEROSIS BY INDUCING INFLAMMATORY MONOCYTE DIFFERENTIATION IN A HYPERGLYCEMIC MOUSE MODEL. [Doctoral Dissertation]. Temple University; 2012. Available from: http://digital.library.temple.edu/u?/p245801coll10,223888


Temple University

2. Meng, Shu. HYPERHOMOCYSTEINEMIA ACCELERATES THROMBOSIS THROUGH ICAM-1 DEPENDENT ENDOTHELIAL ACTIVATION AND DNA HYPOMETHYLATION.

Degree: PhD, 2013, Temple University

Pharmacology

Background: Hyperhomocysteinemia (HHcy) is an established risk factor for thrombotic diseases yet the underlying mechanism remain unclear. In this study we investigated the effect of HHcy on endothelial cell-platelet interaction and its role in thrombosis. Methods and Results: We used a novel mouse model of HHcy (plasma homocysteine, Hcy 80 micromolar) in which a Zn2+ inducible human cystathionine beta-synthase (CBS) transgene was introduced to circumvent the neonatal lethality of the Cbs gene deficiency (Tg-hCBS Cbs-/- mice). Hcy-lowering therapy was performed by giving ZnSO4 water to induce human CBS transgene expression in adult mice. Thrombus formation was examined by photo dye-induced cremaster microvasculature thrombosis using intravital microscopy, in which endothelium was preserved, and by FeCl3-induced carotid artery thrombosis, which denudated the endothelium. HHcy accelerated cremaster arteriolar thrombosis and decreased blood flow cessation time from 41.8 min in control mice to 30.5 min in TghCBS Cbs-/- mice. Venular blood flow cessation time was slightly decreased from 5.6 to 5.0 min. Hcy-lowering therapy reduced Hcy level from 80 micromolar to 6.8 micromolar after 2 weeks of ZnSO4 water and prolonged arteriolar blood cessation time from 30.5 to 37.8 min. Interestingly, FeCl3-induced carotid artery thrombosis did not change the occlusion time. Hcy did not potentiate the aggregation and secretion function in washed human platelets from healthy donor treated with Hcy (50, 100 micromolar) or from Tg-hCBS Cbs-/- mice. However, inter-cellular adhesion molecule 1 (ICAM-1) levels, but not vascular adhesion molecule 1 (VCAM-1), were increased in cremaster tissues from Tg-hCBS Cbs-/- mice by western blot. In cultured human umbilical vein ECs (HUVEC), Hcy (100 micromolar, 24h) promoted human platelet adhesion by 200% in static adhesion assay. Using western blot, FACS and RT-PCR, we found that Hcy increased protein and mRNA levels of ICAM-1, but not that of VCAM-1, in HUVEC. ICAM-1 blocking antibody partially reversed Hcy increased platelets adhesion to HUVEC. Hcy induced ICAM-1 expression and reduced DNA methylation on ICAM-1 promoter, which were mimicked by DNA methyltransferase inhibitor azacytidine, and histone deacetylase inhibitors sodium butyrate and trichostatin A. Hcy treatment also increased intracellular Hcy, Sadenosylhomocysteine (SAH) accumulation and decreased SAM/SAH ratio in HUVECs. Hcy decreased methyl CpG binding protein 2 (MeCP2) binding and increased acetylated histone H3 (AcH3) binding to ICAM-1 core promoter region using chromatin immunoprecipitation. Pyrosequencing of ICAM-1 core promoter and adjacent region shows a decreased DNA methylation by Hcy treatment. In high methionine diet-induce HHcy in WT and Icam-/- mice, Icam-/- mice fed with HM diet only show moderately accelerated venular and barely accelerated arteriolar occlusion time compared with WT mice with CT diet using photo dye-induced thrombosis model. Conclusion: HHcy accelerates arteriolar thrombosis and increases…

Advisors/Committee Members: Wang, Hong;, Ashby, Barrie, Kunapuli, Satya P., Yang, Xiao-Feng, Tuma, Ronald F. (Ronald Franklin), Kruger, Warren D.;.

Subjects/Keywords: Pharmacology;

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

APA (6th Edition):

Meng, S. (2013). HYPERHOMOCYSTEINEMIA ACCELERATES THROMBOSIS THROUGH ICAM-1 DEPENDENT ENDOTHELIAL ACTIVATION AND DNA HYPOMETHYLATION. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,234268

Chicago Manual of Style (16th Edition):

Meng, Shu. “HYPERHOMOCYSTEINEMIA ACCELERATES THROMBOSIS THROUGH ICAM-1 DEPENDENT ENDOTHELIAL ACTIVATION AND DNA HYPOMETHYLATION.” 2013. Doctoral Dissertation, Temple University. Accessed October 22, 2020. http://digital.library.temple.edu/u?/p245801coll10,234268.

MLA Handbook (7th Edition):

Meng, Shu. “HYPERHOMOCYSTEINEMIA ACCELERATES THROMBOSIS THROUGH ICAM-1 DEPENDENT ENDOTHELIAL ACTIVATION AND DNA HYPOMETHYLATION.” 2013. Web. 22 Oct 2020.

Vancouver:

Meng S. HYPERHOMOCYSTEINEMIA ACCELERATES THROMBOSIS THROUGH ICAM-1 DEPENDENT ENDOTHELIAL ACTIVATION AND DNA HYPOMETHYLATION. [Internet] [Doctoral dissertation]. Temple University; 2013. [cited 2020 Oct 22]. Available from: http://digital.library.temple.edu/u?/p245801coll10,234268.

Council of Science Editors:

Meng S. HYPERHOMOCYSTEINEMIA ACCELERATES THROMBOSIS THROUGH ICAM-1 DEPENDENT ENDOTHELIAL ACTIVATION AND DNA HYPOMETHYLATION. [Doctoral Dissertation]. Temple University; 2013. Available from: http://digital.library.temple.edu/u?/p245801coll10,234268

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