Low-Density Lipoprotein in Hypercholesterolemic Human Plasma Induces Vascular Endothelial Cell Apoptosis by Inhibiting Fibroblast Growth Factor 2 Transcription

Abstract

Background— Apoptosis of vascular endothelial cells (ECs) can be induced in vitro by experimentally modified LDL. Description of proapoptotic circulating lipoproteins may significantly enhance understanding of atherothrombosis pathophysiology. Methods and Results— Fast protein liquid chromatography of LDL samples from 7 asymptomatic, hypercholesterolemic patients yielded subfractions L1–L5 in increasing electronegativity. L4 and L5 were not detectable or collectible in normolipidemic samples. In bovine aortic EC cultures, L5 induced marked apoptosis and L4 had a mild effect, whereas hypercholesterolemic or normolipidemic L1–L3 had negligible effects. Compared with copper-oxidized LDL, L5 was only mildly oxidized, although its propensity to form conjugated dienes in response to copper exceeded that of other subfractions. L5-induced apoptosis was associated with suppressed fibroblast growth factor 2 (FGF-2) transcription, as assessed by nuclear run-on analysis. Degrading platelet-activating factor (PAF)-lik...