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Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
Published on: January 28, 2021
Relationship between apolipoprotein C-III concentrations and high-density lipoprotein subclass distribution
1Laboratory of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People's Republic of China.
Insights
Apolipoprotein C-III influences high-density lipoprotein (HDL) subclass distribution, shifting particle size towards smaller forms. Elevated levels, particularly with apo C-II, reduce large HDL particles, impacting antiatherogenic potential.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Biochemistry
Background:
- High-density lipoprotein (HDL) subclasses possess varying antiatherogenic properties.
- Understanding the metabolic regulation of HDL subclasses is crucial for cardiovascular health.
Purpose of the Study:
- To investigate the metabolic implications of apolipoprotein (apo) C-III on HDL subclass distribution.
- To examine the relationship between apo C-III levels, other apolipoproteins, and HDL subclass profiles.
Main Methods:
- Quantification of apolipoprotein A-I in plasma HDL subclasses using 2D gel electrophoresis and immunodetection in 511 subjects.
- Analysis of lipid profiles, including triglycerides, HDL cholesterol, and various apolipoproteins (apo B-100, C-II, C-III).
Main Results:
- Elevated apo C-III levels were associated with a hypertriglyceridemic lipid profile and a shift towards smaller HDL subclasses (prebeta(1)-HDL, HDL(3a/b/c)) and reduced large HDL subclasses (HDL(2a/b)).
- Simultaneous elevation of apo C-III and apo C-II further decreased large HDL(2b) particles and increased small prebeta(1)-HDL.
- Higher apo A-I levels could mitigate the effect of apo C-III on HDL subclass distribution, while low apo A-I exacerbated the reduction of HDL(2b) in hypertriglyceridemic subjects.
Conclusions:
- Plasma apo C-III levels significantly influence HDL subclass distribution, promoting smaller particles and diminishing larger, potentially more protective, HDL species.
- The interplay between apo C-III, apo C-II, and apo A-I levels dictates HDL subclass remodeling, with implications for hypertriglyceridemia and cardiovascular risk.
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 prebeta(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 prebeta(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 prebeta(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 prebeta(1)-HDL, prebeta(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.
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