Angiotensin (Ang) II contributes to the formation and development of myocardial fibrosis. Ghrelin, a gut peptide, has demonstrated beneficial effects against cardiovascular disease. In the present study, we explored the effect and related mechanism of Ghrelin on myocardial fibrosis in Ang II-infused rats. Adult Sprague-Dawley (SD) rats were divided into 6 groups: Control, Ang II (200ng/kg/min, microinfusion), Ang II+Ghrelin (100 mu g/kg, subcutaneously twice daily), Ang II+Ghrelin+GW9662 (a specific PPAR-y inhibitor, 1 mg/kg/d, orally), Ang II+GW9662, and Ghrelin for 4 wks. In vitro, adult rat cardiac fibroblasts (CFs) were pretreated with or without Ghrelin, Ghrelin+GW 9662, or anti-Transforming growth factor (TGF)-beta 1 antibody and then stimulated with or without Ang II (100 nmol/L) for 24 h. Ang II infusion significantly increased myocardial fibrosis, expression of collagen collagen III, and TGF-beta 1, as well as TGF-beta 1 downstream proteins p-Smad2, p-Smad3, TRAF6, and p-TAK1 (all p<0.05). Ghrelin attenuated these effects. Similar results were seen in Ang II-stimulated rat cardiac fibroblasts in vitro. In addition, Ghrelin upregulated PPAR-gamma expression in vivo and in vitro, and treatment with GW9662 counteracted the effects of Ghrelin. In conclusion, Ghrelin ameliorated Ang II-induced myocardial fibrosis by upregulating PPAR-gamma and in turn inhibiting TGF-beta 1 signaling.
[1]Jilin Univ, China Japan Union Hosp, Dept Cardiol, Changchun 130033, Jilin, Peoples R China.
[2]Jilin Prov Peoples Hosp, Changchun 130021, Jilin, Peoples R China.
[3]Baohua Hosp Nongan Cty, Nongan 130200, Peoples R China.
[4]Changchun Univ Chinese Med, Coll Pharm, Changchun 130021, Jilin, Peoples R China.
[5]Jilin Univ, Hosp 1, Changchun 130021, Jilin, Peoples R China.
[6]Tradit Med Inst Jilin Prov, Changchun 130021, Jilin, Peoples R China.
(8.0+极速模式)