D‐4F, an apolipoprotein A‐1 mimetic, inhibit endothelium‐derived microparticles‐induced endothelial nitric oxide synthase dysfunction

Abstract

Endothelium-derived microparticles (EMP) have recently been identified in patients with cardiovascular diseases and are suggested as markers of endothelial dysfunction. D-4F, an apolipoprotein A-1 mimetic, has been reported to improve endothelium- and endothelial nitric oxide synthase (eNOS) dependent vasodilation in a variety of vascular diseases. However, whether D-4F can preserve eNOS function in EMP-treated endothelial cells remains unknown. Bovine aortic endothelial cells (BAEC) were pretreated with EMP (2x106/ml) derived from plasminogen activated inhibitor-1 stimulated human umbilical vein endothelial cells for 30 min. Superoxide anion (O2·–) and nitric oxide (NO) generation were determined. EMP significantly increased O2·– generation where L-nitroargininemethylester partially inhibit it, and decreased NO generation. Western blots show EMP decreased phosphorylation of eNOS with unaltered eNOS expression. However, when BAEC were pretreated with EMP + D-4F 10 μg/ml, D-4F partially restored phosphorylation of eNOS. Our findings indicate D-4F can restore in part, eNOS function in EMP-treated endothelial cell cultures and may provide a new therapeutic approach for treating endothelial dysfunction.