ApoE Containing HDL Subspecies: Their Ability to Inhibit Key Steps in the Atherosclerotic Process

Abstract

Cardiovascular disease is the leading cause of death in people with type-2 diabetes. Cardiovascular disease develops when low-density lipoproteins (LDL) bind to proteoglycans in arterial walls and form atherosclerotic plaques. High-density lipoproteins (HDL) are thought to protect against the development of cardiovascular disease by inhibiting this process. Previous work has shown that HDL exists as numerous subpopulations and that adolescents with type-2 diabetes have decreased apolipoprotein E (apoE) rich large HDL subpopulations compared to lean youth. The goal of this project was to show that decreased amounts of the apoE containing HDL subpopulation is linked to increased risk for cardiovascular disease in type-2 diabetics. Ultracentrifugation and immunoaffinity chromatography were used to isolate the apoE containing large HDL subpopulation from lean and type-2 diabetic adolescents. The composition of these samples was identified using mass spectrometry. Fluorescent proteoglycan binding assays were used to establish if the apoE containing particles from healthy individuals inhibited LDL from binding to a surrogate proteoglycan. Our data support the hypothesis that apoE-containing large HDL subpopulations protect against atherosclerosis. Our findings suggest the possibility of preventing cardiovascular disease in diabetic patients by manipulating the apoE containing particles in adolescents to resemble the composition of a healthy individual.