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

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.