Normolipidemic Subjects With Low HDL Cholesterol Levels Have Altered HDL Subpopulations

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.

Enzymatic assessment of cholesterol on electrophoresis gels for estimating HDL size distribution and plasma concentrations of HDL subclasses

“…The main disadvantage of the protein staining by Coomassie blue is that the method cannot be quantitative; to our knowledge, there is no procedure that selectively assesses HDL-total protein in plasma. The protein fraction, particularly apo AI of HDL, has been used for the quantifi cation of HDL subclasses in two-dimensional electrophoresis ( 10 ). Other components of HDL such as phospholipids and triglycerides may also be used in the quantifi cation of subclasses.…”

“…NMR, vertical autoprofi le-II (VAP-II), as well as selective precipitation are based on HDL lipid content for estimating subclasses ( 5,8,17,18 ), whereas protein is the HDL component determined in other methods, such as two-dimensional electrophoresis ( 10 ) and PAGE in native conditions ( 17 ). Because small HDL particles are protein rich and lipid poor, whereas large particles are the contrary, the relative proportion of HDL subclasses is dependent on the component determined for the quantification.…”

The association between dyslipidemia and anthropometric indicators in black and white adolescents residing in Tlokwe Municipality, North-West Province, South Africa: the PAHL study

“…Others have also revealed that low HDL-C levels are independent risk factors for atherosclerotic vascular disease 30 . It has been reported that individuals with low HDL-C have an abnormal HDL sub-class distribution, with lower levels of large particles and increased levels of small HDL 31 . This abnormality in HDL sub-populations is associated with CHD prevalence 32 and increased recurrence of coronary events 33 .…”

Apolipoprotein composition of HDL in cholesteryl ester transfer protein deficiency

“…Two-dimensional nondenaturing agarose-polyacrylamide gel electrophoresis and image analysis to determine the apoA-I-containing HDL subpopulations were carried out on plasma previously stored at Ϫ 80 Њ C as described (20,21). Briefly, in the first dimension, HDL particles were separated on an agarose gel according to charge.…”