Ginsenoside Re regulates PFKFB3-mediated glycolysis to inhibit endothelial cell migration to ameliorate...

Atherosclerosis (AS) is a major cause of severe cardiovascular disease and stroke. Ginsenoside Re (Re) has been shown to significantly alleviate AS in mice. Our study demonstrates for the first time that Re can reduce endothelial cell (EC) glycolysis, although the specific mechanism remains unclear.

The effects of Re on lipid levels, aortic wall thickness, inflammation, and aortic fibrosis in AS mice were assessed by measuring serum lipids, carotid artery intima-media thickness, Hematoxylin-Eosin, Masson, and Oil Red O staining, and enzyme-linked immunosorbent assay. The effects of Re on EC proliferation and migration were examined using CCK-8 and wound healing assays in a human umbilical vein endothelial cell model stimulated with oxidized low-density lipoprotein. Furthermore, immunohistochemistry, Western blotting, and real-time quantitative polymerase chain reaction were used to investigate the PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways in vivo and in vitro.

Re demonstrated strong anti-AS activity, evidenced by improved blood lipid profiles, reduced inflammatory factors, and decreased levels of glycolysis-related products and enzymes. In vivo, Re protected against AS by inhibiting glycolysis. In vitro, Re suppressed EC migration through inhibition of the glycolysis-related PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways.

Re may benefit AS mice by inhibiting EC glycolysis and migration through suppression of the PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways. This work broadens the theoretical basis for the therapeutic use of Re in AS.