High density lipoprotein subspecies and the control of lipoprotein metabolism in relation to coronary heart disease
The concept that high plasma concentrations of high density lipoproteins (HDL) offers protection against coronary heart disease has been challenged on epidemiological grounds. This dispute may arise as a result of the heterogeneous nature of HDL in which only some subspecies exert a protective function while the major portion has a neutral role. In order to test this hypothesis, the distribution of HDL subfractions in 100 myocardial infarction (MI) survivors was examined within 12 hours of the onset of chest pain and before post-MI changes in lipoproteins occurred. These patients were shown to have a significantly lower percentage distribution of apoprotein E-rich HDL measured by heparin-Sepharose affinity chromatography, and of HDL2b estimated by gradient gel electrophoresis, yet a higher percentage distribution of HDL3c than a similarly sized group of healthy control subjects. At six months post-MI follow-up with an appropriate improvement in lifestyle, as well as therapeutic treatment, there was a significant increase in the percentage distribution of apoprotein E-rich HDL and of HDL2b and a significant decrease in HDL3c, with no alteration in total HDL or any other lipoprotein component. Measurement of these HDL subfractions may thus provide a better indicator of coronary risk than of total plasma cholesterol, which is frequently employed for this purpose, but was found indistinguishable between the two groups in the present study. Such subfractions also provide useful information into the underlying causes of atherosclerosis. The apoprotein E-rich subfraction of HDL which was shown to be reduced in MI survivors, was further separated into several, more discrete subfractions by heparin-Sepharose affinity chromatography, using a judicious choice of eluting solvents. The separated subfractions differed in mean particle diameter and in lipid and apoprotein composition. The fraction designated HDL2b was shown to comprise three main species which may serve different roles in coronary protection.