کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6162704 | 1249402 | 2013 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Simvastatin reduces venous stenosis formation in a murine hemodialysis vascular access model
ترجمه فارسی عنوان
سیمواستاتین تشکیل سلولهای وریدی در یک مدل دسترسی به عروق همودیالیزی موش را کاهش می دهد
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کلمات کلیدی
فیستول شریانی بیماری مزمن کلیوی، مدل موی چتری استشمام رگها،
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
چکیده انگلیسی
Venous neointimal hyperplasia (VNH) is responsible for hemodialysis vascular access malfunction. Here we tested whether VNH formation occurs, in part, due to vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase (MMP)-9 gene expression causing adventitial fibroblast transdifferentiation to myofibroblasts (α-SMA-positive cells). These cells have increased proliferative and migratory capacity leading to VNH formation. Simvastatin was used to decrease VEGF-A and MMP-9 gene expression in our murine arteriovenous fistula model created by connecting the right carotid artery to the ipsilateral jugular vein. Compared to fistulae of vehicle-treated mice, the fistulae of simvastatin-treated mice had the expected decrease in VEGF-A and MMP-9 but also showed a significant reduction in MMP-2 expression with a significant decrease in VNH and a significant increase in the mean lumen vessel area. There was an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and decreases in α-SMA density, cell proliferation, and HIF-1α and hypoxyprobe staining. This latter result prompted us to determine the effect of simvastatin on fibroblasts subjected to hypoxia in vitro. Simvastatin-treated fibroblasts had a significant decrease in myofibroblast production along with decreased cellular proliferation, migration, and MMP-9 activity but increased caspase 3 activity suggesting increased apoptosis. Thus, simvastatin results in a significant reduction in VNH, with increase in mean lumen vessel area by decreasing VEGF-A/MMP-9 pathway activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 84, Issue 2, August 2013, Pages 338-352
Journal: Kidney International - Volume 84, Issue 2, August 2013, Pages 338-352
نویسندگان
Rajiv Janardhanan, Binxia Yang, Pawan Vohra, Bhaskar Roy, Sarah Withers, Santanu Bhattacharya, Jaywant Mandrekar, Hyunjoon Kong, Edward B. Leof, Debabrata Mukhopadhyay, Sanjay Misra,