HDL biology
A review proposes CETP as the mechanistic switch converting protective HDL2 into atherogenic lipoproteins when triglyceride-rich particles accumulate (Atherosclerosis 1994)
Original title: Triglyceride-rich lipoproteins and atherosclerosis
Plasma triglyceride-rich lipoproteins relate to HDL cholesterol and coronary artery disease risk, with a causalist view holding that HDL protects against atherosclerosis and a non-causalist view holding that HDL levels reflect triglyceride-rich lipoprotein metabolism. HDL exists as two subfractions, small dense HDL3 and larger less-dense HDL2. Rapid lipolysis of triglyceride-rich lipoproteins increases lipid uptake and forms HDL2, while delayed lipolysis increases triglyceride transfer into HDL. CETP catalyzes this lipid exchange and may be the mechanism switching good cholesterol into bad cholesterol, with triglyceride-rich lipoprotein metabolism as the driving force. Rapid clearance of triglyceride-rich lipoproteins promotes HDL2 formation and keeps HDL cholesterol high by preventing transfer of HDL cholesteryl esters into triglyceride-rich lipoproteins, an antiatherogenic effect, whereas accumulation of triglyceride-rich lipoproteins drives cholesteryl ester transfer from HDL into high-risk lipoprotein fractions.
Original 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 HDL3, and larger, lipid-rich, less dense HDL2, with variable levels of total-HDL cholesterol. Rapid lipolysis of TG-rich lipoproteins produces increased lipid uptake, formation of HDL2 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 HDL2, 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.