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Diagnostic Pathology
Published in: Diagnostic Pathology 1/2015

Open Access 01-12-2015 | Research

Valsartan blocks thrombospondin/transforming growth factor/Smads to inhibit aortic remodeling in diabetic rats

Authors: Hui Sun, Yong Zhao, Xiuping Bi, Shaohua Li, Guohai Su, Ya Miao, Xiao Ma, Yun Zhang, Wei Zhang, Ming Zhong

Published in: Diagnostic Pathology | Issue 1/2015

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Abstract

Background

Angiotensin II (Ang II) and transforming growth factor β (TGFβ) are closely involved in the pathogenesis of diabetic complications. We aimed to determine whether an aberrant thrombospondin 1 (TSP1)–mediated TGFβ1/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 TGFβ1/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 TGFβ1/Smads signaling pathway, including TSP1, TGFβ1, TGFβ type II receptor (TβRII), 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 TGFβ1/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.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​1053842818141195​
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Metadata
Title
Valsartan blocks thrombospondin/transforming growth factor/Smads to inhibit aortic remodeling in diabetic rats
Authors
Hui Sun
Yong Zhao
Xiuping Bi
Shaohua Li
Guohai Su
Ya Miao
Xiao Ma
Yun Zhang
Wei Zhang
Ming Zhong
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2015
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-015-0246-8

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