Triglyceride-rich lipoproteins and atherosclerosis

Abstract

Plasma triglyceride (TG)-rich lipoproteins are related to high density lipoprotein (HDL)-cholesterol and risk of coronary artery disease (CAD). Two major hypotheses on the role of HDL in the development of CAD have been proposed: a ‘causalist’ view assigns a protective effect against atherosclerosis to HDL and a ‘non-causalist’ view states that HDL do not interfere directly with development of atheroma but reflect metabolism of TG-rich lipoproteins. HDL exist as two major subfractions: small, lipid-poor, dense HDL 3, and larger, lipid-rich, less dense HDL 2, with variable levels of total-HDL cholesterol. Rapid lipolysis of TG-rich lipoproteins produces increased lipid uptake, formation of HDL 2 and may protect the arterial wall; delayed lipolysis increases transfer of TG from TG-rich lipoproteins into HDL. Cholesteryl ester transfer protein (CETP) catalyzes lipid exchange and may be the mechanism for switching ‘good cholesterol’ into ‘bad cholesterol’. According to this view, the driving force for the switch is the metabolism of TG-rich lipoproteins. Rapid clearance of TG-rich lipoproteins promotes formation of HDL 2, low levels of TG-rich lipoproteins prevent transfer of HDL-cholesteryl esters into TG-rich lipoproteins keeping HDL-cholesterol high. The net effect is antiatherogenic. Accumulation of TG-rich lipoproteins leads to transfer of cholesteryl esters from HDL into lipoprotein fractions associated with high CAD risk.