Valsartan blocks thrombospondin/transforming growth factor/Smads to inhibit aortic remodeling in diabetic rats
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摘要
Background: Angiotensin II (Ang II) and transforming growth factor beta (TGF beta) are closely involved in the pathogenesis of diabetic complications. We aimed to determine whether an aberrant thrombospondin 1 (TSP1)-mediated TGF beta 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 beta 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 beta 1/Smads signaling pathway, including TSP1, TGF beta 1, TGF beta type II receptor (T beta 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 beta 1/Smads pathway activation plays an important role in marcovascular remodeling in T2DM in rat. Valsartan can block the pathway and ameliorate vascular fibrosis.
关键词
EXTRACELLULAR-MATRIX PRODUCTION; BLOOD-PRESSURE CONTROL; HUMAN MESANGIAL CELLS; TGF-BETA; ANGIOTENSIN-II; CARDIOVASCULAR OUTCOMES; MICROVASCULAR OUTCOMES; RANDOMIZED-TRIAL; VESSEL WALL; THROMBOSPONDIN-1
基本信息
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所属机构:
归属医师: 赵勇 李少华
PMID:25884585
UT:000369640800001
刊名:DIAGNOSTIC PATHOLOGY
年,卷(期):2015年10卷
DOI:10.1186/s13000-015-0246-8
附件:
收录: SCIE