Evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, promotes angiogenesis in vitro

Abstract

The proprotein convertases family is involved in several physiological processes such as cell growth, migration, and angiogenesis, and also in different pathological conditions. Evolocumab, an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), has recently been approved for treatment of hypercholesterolemia. This study aimed to investigate the effect of evolocumab on angiogenesis in human umbilical vein endothelial cells (HUVECs). Cell proliferation and migration were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell methods. In vitro angiogenesis was assessed by tube formation assay. Vascular endothelial growth factor (VEGF) secretion by HUVECs was also determined using an enzyme-linked immunosorbent assay kit. Evolocumab significantly increased HUVECs viability at 100 mu g/mL. Significant enhancement in cell migration, and mean tubules length and size was observed at the concentrations of 10 and 100 mu g/mL and also in mean number of junctions at the concentration of 100 mu g/mL. Administration of evolocumab at the concentration of 10 mu g/mL increased VEGF release into supernatants of HUVECs. Findings of this investigation provided in vitro evidence for pro-angiogenic activity of evolocumab through promoting cell proliferation, migration, tubulogenesis, and VEGF secretion in HUVECs.