LDL subfractions and atherogenicity: an hypothesis from the University of Glasgow

The variation in the size and atherogenicity of the low density lipoprotein (LDL) particles has attracted a great deal of recent attention. In particular, attention has focused on the role of plasma triglyceride concentrations in driving the lipoprotein exchange that determines the concentration of the smaller, denser, more atherogenic LDL fraction. In a study at Glasgow University, researchers analysed the distribution of LDL subfractions among normocholesterolaemic men, with or without coronary artery disease, survivors of myocardial infarction, and normal controls. The results showed that the risk of coronary artery disease or myocardial infarction is considerably greater in those groups with higher plasma concentrations of small, dense LDL. In a second study, eight patients with hypercholesterolaemia were treated with fenofibrate. Radioisotope tracers showed that fenofibrate shifts the distribution of LDL subfractions from small, dense, atherogenic particles towards larger, lighter, less atherogenic ones. The efficacy of fenofibrate derives from its hypotriglyceridaemic activity. Triglycerides may have further atherogenic and thrombogenic effects: they may cause endothelial cell dysfunction in the artery wall, stimulating the recruitment of macrophages into the endothelium. They may also promote the synthesis of thrombogenic mediators, suppressing local plasmin synthesis and accelerating intra-arterial fibrin deposition. This evidence has led to an increasing recognition of the central role of triglycerides in the process of atherogenesis.