The metabolism and anti-atherogenic properties of HDL

Abstract

Population studies have shown that plasma HDL levels correlate inversely with cardiovascular disease risk. In recent years there has been intense interest in developing strategies for exploiting these cardioprotective properties by increasing HDL levels. While this approach has considerable merit, it is important to recognize that HDL are structurally and functionally diverse and consist of numerous, highly dynamic subpopulations of particles that do not all inhibit atherosclerosis to the same extent. For this reason it is essential to assess HDL subpopulation distribution and functionality when considering therapeutic interventions that raise HDL levels. This review documents what is known about the relationship between the metabolism and function of HDL subpopulations and how this affects their cardioprotective properties.

Fig. 1.

HDL heterogeneity. The HDL in human plasma consist of several subpopulations of particles that vary widely in shape (A), density (B), size (C), composition (D), and surface charge (E).

Fig. 2.

HDL Remodelling. Influence of plasma factors on the subpopulation distribution of HDL. LCAT generates cholesteryl esters and remodels discoidal HDL into spherical HDL (i); cholesteryl ester transfer protein (CETP) transfers cholesteryl esters and triglycerides between HDL, LDL, and VLDL; remodels HDL into small particles; and generates lipid-free/lipid-poor apoA-I (ii); phospholipid transfer protein (PLTP) transfers phospholipids between HDL and VLDL and between individual HDL particles; remodels HDL into large and small particles; and generates lipid-free/lipid-poor apoA-I (iii); endothelial lipase (EL) hydrolyses phospholipids and remodels HDL into small particles(iv); and hepatic lipase (HL) hydrolyses phospholipids and triglycerides, remodels HDL into small particles, and generates lipid-free/lipid-poor apoA-I (v).