A Helping Hand for the Good Guy; Novel Pharmacological Approaches for Augmenting the Cardiovascular Benefits of High Density Lipoproteins

Richard   W.   James

Abstract

Pharmacological modulation of serum lipid levels is a powerful means of favourably modifying the risk and incidence of coronary disease. High density lipoproteins (HDL) exert a beneficial influence on atherosclerotic disease, in part by modulating blood lipid metabolism. Three factors have contributed to the growing interest in HDL as a therapeutic target. Firstly, recent, if limited, clinical trials have demonstrated the cardiovascular benefits of modulating HDL. Secondly, on-going studies have clarified several aspects of HDL metabolism and opened new avenues for pharmacological intervention. Thirdly, the WHO foresees an enormous global increase in the incidence of type 2 diabetes, as well as a related disorder, the metabolic syndrome. Both have, as their primary complication, cardiovascular disease whilst one of the principal lipid disorders is a reduction in HDL. Thus for several cogent reasons, HDL has become a primary target for drug development. The review covers our understanding of HDL metabolism, and notably the contribution of recent studies, in the context of potential sites for intervention. The rationale for targeting such sites, and available human and animal data on the cardiovascular consequences of modulating their activities, is discussed. Finally, the current status of drugs developed with a view to influencing HDL metabolism is presented.

Keywords: lipoproteins, atherosclerosis, cholesterol, triglycerides, risk, hdl, ldl, vascular, gene