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Basic science: Cardiovascular disease basic research
e0052 Valsartan reversed vascular fibrosis through the blockade of the AT1-mediated TGF-β/Smad signal pathway in the fat-fed, streptozotocin-treated rats
  1. Sun Hui,
  2. Zhang Wei,
  3. Zhong Ming,
  4. Zhao Yong,
  5. Su Guohai,
  6. Zhang Yun
  1. The Key Laboratory of Cardiovascular Remodelling And Function Research, Chinese Ministry of Education And Chinese Ministry of Public Health, Shandong University, Qilu Hospital, Ji'nan, China

Abstract

Objective Angiotensin II (AII) and transforming growth factor-β (TGF-β) are closely involved in the pathogenesis of diabetic complications. The aim of this study was to clarify the role of AII in the regulation of the TGF-β system in diabetic vascular dysfunction.

Methods Male Wistar rats were randomly divided into three groups : normal control, diabetic rats and valsartan group. Diabetes was induced by high-calorie diet for 4 weeks and a single intraperitoneal injection of streptozotocin (STZ) thereafter. The expression of TGF-β1/Smads signalling was analysed by real-time reverse transcriptase-PCR and immunohistochemistry in aorta of three groups.

Results Compared with control group, the expression of both TGF-β I (27.4013±10.49256 vs 15.1254±6.64343, p<0.01), TGF-β receptor types II (28.0173±10.22042 vs 10.0561±8.22275, p<0.01) and activation of the smad2/3 (31.4029±10.44721 vs 12.8769±6.98547, p<0.001) signalling pathway were up-regulated in the vasculature in diabetic rats. Compared with diabetic group, active TGF-β (18.5682±10.29359 vs 27.4013±10.49256, p<0.05) and Smad2/3 (20.5209±7.82756 vs 31.4029±10.44721, p<0.01) protein levels were reduced in the aorta after the treatment of valsartan.

Conclusions Our results suggest that AT1 receptor antagonist has reversed vascular fibrosis through the blockade of the AT1-mediated TGF-β/Smad signal pathway in the diabetic rats with vascular dysfunction. These observations may del support additional, beneficial effects of angiotensin receptor antagonists observed during del diabetic vascular complications.

  • Valsartan reversed vascular fibrosis
  • Blockade
  • AT1-mediated
  • TGF-β/Smad signal pathway
  • fat-fed
  • Streptozotocin-treated rats

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