Altered Lipid Composition, Increased Susceptibility for Sphingomyelinase, and Increased Binding to Biglycan

OBJECTIVE—Apolipoprotein CIII (apoCIII) is an independent risk factor for cardiovascular disease, but the molecular mecha-nisms involved are poorly understood. We investigated potential proatherogenic properties of apoCIII-containing LDL from hyper-triglyceridemic patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—LDL was isolated from control subjects, subjects with type 2 diabetes, and apoB transgenic mice. LDL-biglycan binding was analyzed with a solid-phase assay using immunoplates coated with biglycan. Lipid composition was analyzed with mass spectrometry. Hydro-lysis of LDL by sphingomyelinase was analyzed after labeling plasma LDL with [3H]sphingomyelin. ApoCIII isoforms were quantified after isoelectric focusing. Human aortic endothelial cells were incubated with desialylated apoCIII or with LDL enriched with specific apoCIII isoforms