HDL biology
Low-HDL-cholesterol normolipidemic men show a shift from alpha1 to alpha3 HDL subpopulations, possibly via CETP-driven interconversion (Arterioscler Thromb Vasc Biol 1997)
Original title: Normolipidemic subjects with low HDL cholesterol levels have altered HDL subpopulations
HDL subpopulations were quantified by two-dimensional gel electrophoresis in 79 normolipidemic healthy men who consumed a standardized diet for 6 weeks, then were stratified by HDL cholesterol (HDL-C) into low (< 0.91 mmol/L), medium (0.91 to 1.30 mmol/L), and high (>= 1.30 mmol/L) groups. Subjects with low HDL-C had higher plasma triglycerides and insulin than those with medium or high HDL-C. Absolute apoA-I in the largest alpha-migrating subpopulation (alpha1) was lower in low HDL-C subjects (P < .01), while relative apoA-I was decreased in alpha1 and increased in alpha3 (both P < .01). HDL-C correlated positively with alpha1 (P < .001) and negatively with alpha3. This inverse relationship between alpha1 and alpha3 apoA-I distribution suggests an interconversion of these subpopulations, possibly mediated by cholesteryl ester transfer protein.
Original 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 < 0.91 mmol/L (< 35 mg/dL), medium > 0.91 < 1.30 mmol/L (> 35 < 50 mg/dL), and high > or = 1.30 mmol/L (> or = 50 mg/dL) groups. Plasma triglycerides and insulin levels were in the normal 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) 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 alpha 1 and increased (P < .01) in alpha 3 subpopulations. 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 concentration) 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-migrating subpopulation. Colocalization of apoA-I and apoA-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 than apoA-I:A-II particles.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.