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Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Diagn+Pathol 2015 ; 10 (ä): ä Nephropedia Template TP
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Valsartan blocks thrombospondin/transforming growth factor/Smads to inhibit aortic remodeling in diabetic rats #MMPMID25884585
Sun H; Zhao Y; Bi X; Li S; Su G; Miao Y; Ma X; Zhang Y; Zhang W; Zhong M
Diagn Pathol 2015[]; 10 (ä): ä PMID25884585show ga
Background: Angiotensin II (Ang II) and transforming growth factor ? (TGF?) are closely involved in the pathogenesis of diabetic complications. We aimed to determine whether an aberrant thrombospondin 1 (TSP1)?mediated TGF?1/Smads signaling pathway specifically affects vascular fibrosis in diabetic rats and whether valsartan, an Ang II subtype 1 receptor blocker, has an anti-fibrotic effect. Methods: Age-matched male Wistar rats were randomly divided into 3 groups: control (n?=?8), diabetes (n?=?16) and valsartan (30 mg/kg/day) (n?=?16). Type 2 diabetes mellitus (T2DM) was induced by a high-calorie diet and streptozotocin injection. Morphological and biomechanical properties of the thoracic aorta were assessed by echocardiography and cardiac catheterization. Masson staining was used for histological evaluation of extracellular matrix (ECM). The expression of components in the TSP1?mediated TGF?1/Smads signaling pathway was analyzed by immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction. Results: As compared with controls, diabetic aortas showed reduced distensibility and compliance, with excess ECM deposition. Components in the TSP1-mediated TGF?1/Smads signaling pathway, including TSP1, TGF?1, TGF? type II receptor (T?RII), Smad2 and Smad3, were accumulated in vascular smooth muscle cytoplasm of diabetic aortas and their protein and mRNA levels were upregulated. All these abnormalities were attenuated by valsartan. Conclusions: TSP1-mediated TGF?1/Smads pathway activation plays an important role in marcovascular remodeling in T2DM in rat. Valsartan can block the pathway and ameliorate vascular fibrosis. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1053842818141195