Ghrelin Ameliorates Angiotensin II-Induced Myocardial Fibrosis by Upregulating Peroxisome Proliferator-Activated Receptor Gamma in Young Male Rats

Abstract EN

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 μg/kg, subcutaneously twice daily), Ang II+Ghrelin+GW9662 (a specific PPAR-γ 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+GW9662, or anti-Transforming growth factor (TGF)-β1 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 I, collagen III, and TGF-β1, as well as TGF-β1 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-γ 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-γ and in turn inhibiting TGF-β1signaling.