Yeast-derived β-glucan enhances angiogenesis by activating the AMPK-HDAC7-MEF2 axis

Angiogenesis, the process by which new blood vessels from pre-existing vasculature, is essential for tissue repair, regeneration, and vascular remodeling. Yeast-derived β-glucans exhibit potent immunomodulatory properties, and recently, they have gained increasing attention for their potential vascular effects. However, their angiogenic functions and underlying molecular mechanisms remain poorly understood. In the present study, we demonstrated that yeast-derived β-glucan can promote angiogenesis in endothelial cells through the AMP-activated protein kinase (AMPK)-histone deacetylase 7 (HDAC7)-myocyte enhancer factor 2 (MEF2) signaling axis. Specifically, β-glucan activated AMPK phosphorylation and induced phosphorylation-dependent nuclear export of HDAC7. This cytoplasmic translocation resulted in enhanced MEF2 transcriptional activity and upregulation of MEF2-dependent pro-angiogenic genes. Functionally, β-glucan significantly stimulated endothelial migration and tube formation in vitro. It also promoted vessel sprouting in aortic ring assays ex vivo. In vivo, β-glucan induced blood flow recovery in a hindlimb ischemia mouse model. Overall, this study identifies a novel mechanism by which yeast-derived β-glucan regulates angiogenesis, suggesting its therapeutic potential for ischemic cardiovascular disease.