کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5939076 | 1573474 | 2007 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A Thrombospondin-1 Antagonist of Transforming Growth Factor-β Activation Blocks Cardiomyopathy in Rats with Diabetes and Elevated Angiotensin II
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موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
کاردیولوژی و پزشکی قلب و عروق
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چکیده انگلیسی
In diabetes and hypertension, the induction of increased transforming growth factor-β (TGF-β) activity due to glucose and angiotensin II is a significant factor in the development of fibrosis and organ failure. We showed previously that glucose and angiotensin II induce the latent TGF-β activator thrombospondin-1 (TSP1). Because activation of latent TGF-β is a major means of regulating TGF-β, we addressed the role of TSP1-mediated TGF-β activation in the development of diabetic cardiomyopathy exacerbated by abdominal aortic coarctation in a rat model of type 1 diabetes using a peptide antagonist of TSP1-dependent TGF-β activation. This surgical manipulation elevates initial blood pressure and angiotensin II. The hearts of these rats had increased TSP1, collagen, and TGF-β activity, and cardiac function was diminished. A peptide antagonist of TSP1-dependent TGF-β activation prevented progression of cardiac fibrosis and improved cardiac function by reducing TGF-β activity. These data suggest that TSP1 is a significant mediator of fibrotic complications of diabetes associated with stimulation of the renin-angiotensin system, and further studies to assess the blockade of TSP1-dependent TGF-β activation as a potential antifibrotic therapeutic strategy are warranted.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The American Journal of Pathology - Volume 171, Issue 3, September 2007, Pages 777-789
Journal: The American Journal of Pathology - Volume 171, Issue 3, September 2007, Pages 777-789
نویسندگان
Souad Belmadani, Juan Bernal, Chih-Chang Wei, Manuel A. Pallero, Louis Dell'Italia, Joanne E. Murphy-Ullrich, Kathleen H. Berecek,