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
- TGF-β/Smad signal pathway
- Streptozotocin-treated rats