Relationship between apolipoprotein C-III concentrations and high-density lipoprotein subclass distribution

Abstract

High-density lipoprotein (HDL) subclasses have different antiatherogenic potentials and functional properties. This work presents our findings and discussions on their metabolic implications on apolipoprotein (apo) C-III together with other apolipoprotein levels and HDL subclass distribution profile. Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 511 subjects. Concentrations of triglycerides and of apo B-100, C-II, and C-III were higher, whereas those of HDL cholesterol were lower, for subjects in the highest tertile of apo C-III levels group, which presented a typical hypertriglyceridemic lipid profile. Subjects in the middle and highest tertile of apo C-III levels groups had increased pre β 1-HDL, HDL 3c, HDL 3b (only in the highest tertile of apo C-III group), and HDL 3a, but decreased HDL 2a and HDL 2b contents compared with subjects in the lowest tertile of apo C-III levels group. With the elevation of apo C-III together with apo C-II levels, contents of small-sized pre β 1-HDL increased successively and significantly; but those of large-sized HDL 2b reduced successively and significantly. With a rise in apo C-III and apo A-I levels, those of pre β 1-HDL increased significantly. Moreover, subjects with high apo A-I levels showed a substantial increase in HDL 2b; on the contrary, HDL 2b declined progressively and obviously for subjects in the low apo A-I levels with the elevation of apo C-III levels. Correlation analysis illustrated that apo C-III levels were positively associated with pre β 1-HDL, pre β 2-HDL, and HDL 3a. The particle size of HDL shifted toward smaller sizes with the increase of plasma apo C-III levels, and the shift was more remarkable when the elevation of apo C-III and apo C-II was simultaneous; and besides, higher apo A-I concentrations could modify the effect of apo C-III on HDL subclass distribution profile. Large-sized HDL 2b particles decreased greatly for hypertriglyceridemic subjects who were characterized by elevated apo C-III and C-II accompanied with significantly lower apo A-I, which, in turn, blocked the maturation of HDL.