Evolocumab, a PCSK9 inhibitor, protects human endothelial cells against H(2)O(2)-induced oxidative stress

Abstract

CONTEXT: Recent surveys have shown an association between proprotein convertase subtilisin/kexin type 9 (PCSK9) and oxidative stress. OBJECTIVE: In this investigation, the effect of evolocumab an anti-PCSK9 antibody was assessed against oxidative damage caused by hydrogen peroxide (H(2)O(2)) in human umbilical vein endothelial cells (HUVEC). MATERIAL AND METHODS: Viability of HUVEC was measured by MTT assay. Hydroperoxides and malondialdehyde (MDA) levels, and ferric reducing antioxidant power (FRAP) were detected in HUVEC that pre-treated with evolocumab and, then exposed to H(2)O(2). RESULTS: Evolocumab significantly prevented the cytotoxicity induced by H(2)O(2) at the concentrations of 5-100 microg/ml. Pre-treatment of HUVEC with evolocumab reduced hydroperoxides and MDA levels and also increased FRAP value in intra- and extra-cellular mediums compared with H(2)O(2) stimulated cells at different concentration ranges. CONCLUSION: This study displayed anti-oxidative and cytoprotective activities of evolocumab against oxidative damage caused by H(2)O(2) in endothelial cells.