Lipoprotein Metabolism and Atherogenesis

Summary

Understanding lipoprotein heterogeneity is an essential step in the further discovery of the pathogenesis of atherosclerosis and in the tailoring of pharmacologic treatment for subjects at risk. Most individuals who succumb to coronary heart disease do not have frank hyperlipidemia but instead exhibit minor disturbances in their plasma lipid profile. Small, dense low density lipoprotein appears to be a particularly atherogenic lipoprotein species. It is oxidised more easily that its larger counterparts. Further, it has been recently shown that low density lipoprotein from subjects with an atherogenic lipoprotein phenotype binds more readily to arterial wall proteoglycans thus potentially increasing the residence time of the lipoprotein in the arterial wall. However, it should be remembered that the moderate hypertriglyceridemia of the atherogenic lipoprotein profile is associated not only with small dense low density lipoprotein, but also the presence of long-lived remnants of very low density lipoprotein and intermediate density lipoprotein, both of which are believed to contribute to increased risk of coronary heart disease. Thus very low density lipoprotein, if it fails to be cleared efficiently from the circulation, may spawn a cascade of atherogenic lipoproteins. In addition, raised fasting triglyceride levels are a determinant of slow chylomicron clearance and those with an atherogenic lipoprotein profile also accumulate chylomicron remnants in their bloodstream. Understanding the mechanism of generation of the atherogenic lipoprotein may lead to development of drugs that can correct more effectively the underlying disturbance.