Normolipidemic Subjects With Low HDL Cholesterol Levels Have Altered HDL Subpopulations

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Abstract
Abstract Epidemiological studies have established that plasma concentration of HDL is inversely correlated with the risk of coronary heart disease, even in the absence of increased LDL cholesterol levels. We postulate that specific HDL subpopulations may be responsible for antiatherogenic properties of HDL. HDL subpopulations were quantitated by two-dimensional gel electrophoresis in 79 normolipidemic healthy male subjects. To eliminate the influence of diet, volunteers consumed an average American diet for 6 weeks. After the diet period, subjects were stratified according to their HDL cholesterol (HDL-C) levels to low HDL-C 1 ) was ( P <.01) lower in the low HDL-C subjects compared with the medium and high HDL-C groups. The relative concentration (percent distribution) of apoA-I was decreased ( P <.01) in α 1 and increased ( P <.01) in α 3 subpopulations. A positive correlation between HDL-C and α 1 ( P <.001) and a negative correlation between HDL-C and α 3 were observed. The inverse correlation of apoA-I distribution (relative concentration) between α 1 and α 3 suggests an interconversion of α 1 and α 3 subpopulations, possibly by cholesteryl ester transfer protein. Pre-β subpopulations showed an inverse trend with HDL-C, while the pre-α subpopulation behaved similarly to the α-migrating subpopulation. Colocalization of apoA-I and apoA-II particles in the different HDL subpopulations demonstrated that α 1 , pre-β 1 , and pre-β 2 subpopulations are apoA-I–only particles rather than apoA-I:A-II particles.