NORMOLIPIDEMIC SUBJECTS WITH LOW HDL CHOLESTEROL LEVELS HAVE ALTERED HDL SUBPOPULATIONS

Epidemiological studies have established that plasma concentration of HDL is inversely correlated with the risk of coronary heart disease, e ven in the absence of increased LDL cholesterol levels. We postulate t hat specific HDL subpopulations may be responsible for antiatherogenic properties of HDL. HDL subpopulations were quantitated by two-dimensi onal gel electrophoresis in 79 normolipidemic healthy male subjects. T o eliminate the influence of diet, volunteers consumed an average Amer ican diet for 6 weeks. After the diet period, subjects were stratified according to their HDL cholesterol (HDL-C) levels to low HDL-C <0.91 mmol/L (<35 mg/dL), medium >0.91 <1.30 mmol/L (>35 <50 mg/dL), and hig h greater than or equal to 1.30 mmol/L (greater than or equal to 50 mg /dL) groups. Plasma triglycerides and insulin levels were in the norma l range, but subjects with low HDL-C levels had higher concentrations of plasma triglycerides and insulin than subjects with medium or high HDL-C concentrations. The absolute concentration (mg/dL) of apoA-I in the largest alpha-migrating HDL subpopulation (alpha(1)) was (P<.01) l ower in the low HDL-C subjects compared with the medium and high HDL-C groups. The relative concentration (percent distribution) of apoA-I w as decreased (P<.01) in alpha(1) and increased (P<.01) in alpha(3) sub populations. A positive correlation between HDL-C and alpha(1) (P<.001 ) and a negative correlation between HDL-C and alpha(3) were observed. The inverse correlation of apoA-I distribution (relative concentratio n) between alpha(1) and alpha(3) suggests an interconversion of alpha( 1) and alpha(3) subpopulations, possibly by cholesteryl ester transfer protein. Pre-beta subpopulations showed an inverse trend with HDL-C, while the pre-alpha subpopulation behaved similarly to the alpha-migra ting subpopulation. Colocalization of apoA-I and apaA-II particles in the different HDL subpopulations demonstrated that alpha(1), pre-beta( 1), and pre-beta(2) subpopulations are apoA-I-only particles rather th an apoA-I:A-II particles.