Ghrelin/GHSR-1a promotes angiogenesis after myocardial infarction through the glycolytic process

Therapeutic angiogenesis has demonstrated efficacy in revascularizing ischemic heart tissue and reducing the progression of cardiac remodeling following myocardial infarction. Recent studies have highlighted the significance of the glycolytic process in maintaining endothelial cell function and cardiac homeostasis. However, the specific role of glycolysis in angiogenesis post-myocardial infarction remains poorly understood. This study aims to explore whether ghrelin/GHSR-1a promotes angiogenesis after myocardial infarction through glycolysis.

Myocardial infarction was induced in mice, and our experiments showed that GHSR-1a overexpression led to a significant increase in the density of α-SMA-positive vessels in the peri-infarct zones, compared to the MI group, at day 7 post-infarction. Furthermore, elevated FGF-21 levels were observed in the border zone of the infarcted area seven days post-acute myocardial infarction. We also identified a modified GHSR-1a/FGF-21 axis in cardiac endothelial cells, where GHSR-1a knockdown reduced the expression of both FGF-21 and AMPK. In vitro, ghrelin enhanced glycolytic activity by increasing the expression of glycolytic enzymes. Moreover, ghrelin significantly stimulated endothelial tube formation and enhanced cell viability; however, these effects were attenuated following FGF-21 knockdown.

Our findings demonstrate that ghrelin/GHSR-1a improves neovascularization and enhances glycolysis in cardiac endothelial cells by modulating FGF-21. These results lay the groundwork for further experimental and clinical investigations to explore pharmaceutical approaches for treating ischemic heart disease.