Procyanidin B2 attenuates pathological cardiac fibrosis and inflammation: role of PPARγ.

Abstract

Procyanidin B2 (PB2) is a prominent procyanidin isomer. Its effects and mechanisms in cardiac remodeling are not fully understood. Peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a crucial role in regulating cardiac hypertrophy, fibrosis, and inflammation. This study aims to investigate the effect of PB2 on pathological cardiac fibrosis and inflammation, focusing on the underlying mechanisms involving PPAR-γ. In vitro, cardiac fibrosis was induced in cardiac fibroblasts using angiotensin II. In vivo, a mouse model of pathological cardiac fibrosis was generated through transverse aortic constriction to induce pressure overload. We found that PB2 inhibited proliferation, differentiation, collagen accumulation, and the NF-κB inflammation pathway in cardiac fibroblasts triggered by angiotensin II. These inhibitory effects were negated by the PPAR-γ antagonist GW9662 and RNA interference. Additionally, PB2 directly elevated PPAR-γ expression in cardiac fibroblasts. Similarly, PB2 alleviated transverse aortic constriction-induced cardiac dysfunction, myocardial fibrosis, and inflammation in mice. These cardioprotective effects of PB2 in vivo were counteracted by co-administration with GW9662. Correspondingly, the upregulation of PPAR-γ protein expression by PB2 in pressure-overloaded hearts was also counteracted by GW9662 co-administration. In conclusion, this study demonstrates that PB2 exerts protective effects against pathological cardiac fibrosis and inflammation through a PPAR-γ dependent mechanism.