Ginsenoside Rb1 inhibits M1 macrophages-induced IGFBP2-mediated endothelial-mesenchymal transition to alleviate myocardial fibrosis in mice with chronic heart failure.

Abstract

Ginsenoside Rb1 ameliorates renal fibrosis, yet its effects on myocardial fibrosis (MF) remain unclear. In this study, we aimed to explore the role of ginsenoside Rb1 in chronic heart failure (CHF) and MF. To explore the correlation between endothelial-mesenchymal transition (EndMT) in endothelial cells and IGFBP2 expression in M1 macrophages, M1 macrophages were polarized and co-cultured with myocardial microvascular endothelial cells (MMVECs). IGFBP2 levels in the macrophages and levels of endothelial-specific markers and EndMT-related indexes in MMVECs were measured. Additionally, we treated the macrophages with ginsenoside Rb1. The CHF mice model was established using transverse aortic constriction (TAC) and then treated with ginsenoside Rb1. The effects of Rb1 on cardiac function, MF, and cardiomyocyte hypertrophy in CHF mice were assessed. We observed the successful differentiation of M1 macrophages using in vitro experiments. M1 macrophages co-cultured with MMVECs demonstrated the ability to enhance the EndMT effect in MMVECs, as evidenced by elevated levels of IGFBP2 in the macrophages and a reduction in the viability of MMVECs. This decrease in cell viability was mitigated following the knockdown of IGFBP2. Rb1 treatment significantly suppressed the expression of IGFBP2 and inhibited the occurrence of the EndMT in MMVECs. The in vivo experiment findings showed that ginsenoside Rb1 notably enhanced cardiac function, attenuated cardiomyocyte hypertrophy, and alleviated MF in CHF mice. Furthermore, ginsenoside Rb1 inhibited M1 macrophage polarization, reduced IGFBP2 expression in the myocardium, and suppressed the EndMT effect of MMVECs in mice. Ginsenoside Rb1 alleviated MF in mice with CHF by inhibiting M1 macrophage IGFBP2-mediated EndMT.