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Distribution of ApoA-I-containing HDL subpopulations in patients with coronary heart disease
B F Asztalos1, P S Roheim, R L Milani
1Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Center on Aging at Tufts University, Boston, MA 02111, USA. belaasztalos@yahoo.com
Insights
Coronary heart disease patients show lower levels of large, beneficial high density lipoprotein (HDL) subpopulations and higher levels of small HDL particles. These changes in HDL subspecies are more pronounced than overall HDL cholesterol reduction, indicating a significant rearrangement in HDL composition.
Area of Science:
- Cardiovascular Science
- Lipidology
- Biochemistry
Background:
- High density lipoproteins (HDLs) and their subspecies are implicated in coronary heart disease (CHD) development.
- Traditional lipid levels may not fully capture the complexity of HDL's role in CHD.
Purpose of the Study:
- To investigate differences in apolipoprotein (apo)A-I-containing HDL subpopulations between male CHD patients and control subjects.
- To compare the discriminatory power of HDL subspecies versus traditional lipid levels in identifying CHD.
Main Methods:
- Two-dimensional nondenaturing gel electrophoresis was used to measure HDL subpopulations.
- HDL subspecies were analyzed in 79 male control subjects and 76 male CHD patients.
Main Results:
- CHD subjects had lower HDL cholesterol and higher total cholesterol/HDL-C ratios but similar apoA-I and LDL cholesterol levels compared to controls.
- Significant reductions in large LpA-I subpopulations (alpha(1), pre-alpha(1-3)) and an increase in small LpA-I/A-II alpha(3) particles were observed in CHD patients.
- Ratios of HDL-C to alpha(1) and apoA-I to alpha(1) were significantly higher in CHD subjects, even after matching for HDL-C levels.
Conclusions:
- Coronary heart disease patients exhibit not only HDL deficiency but also a significant alteration in HDL subpopulation distribution.
- The shift towards smaller, potentially less atheroprotective HDL particles (LpA-I/A-II) and away from larger, atheroprotective particles (LpA-I) is a key characteristic of CHD.
- HDL subspecies analysis provides a more sensitive marker for CHD than traditional lipid profiles.
Abstract:
High density lipoproteins (HDLs) and their subspecies play a role in the development of coronary heart disease (CHD). HDL subpopulations were measured by 2-dimensional nondenaturing gel electrophoresis in 79 male control subjects and 76 male CHD patients to test the hypothesis that greater differences in apolipoprotein (apo)A-I-containing HDL subpopulations would exist between these 2 groups than for traditional lipid levels. In CHD subjects, HDL cholesterol (HDL-C) was lower (-14%, P<0.001), whereas total cholesterol and the low density lipoprotein cholesterol/HDL-C ratio were higher (9% [P:<0.05] and 21% [P:<0.01], respectively) compared with control levels. No significant differences were found for low density lipoprotein cholesterol, triglyceride, and apoA-I levels. In CHD subjects, there were significantly (P:<0.001) lower concentrations of the large lipoprotein (Lp)A-I alpha(1) (-35%), pre-alpha(1) (-50%), pre-alpha(2) (-33%), and pre-alpha(3) (-31%) subpopulations, whereas the concentrations of the small LpA-I/A-II alpha(3) particles were significantly (P:<0.001) higher (20%). Because alpha(1) was decreased more than HDL-C and plasma apoA-I concentrations in CHD subjects, the ratios of HDL-C to alpha(1) and of apoA-I to alpha(1) were significantly (P:<0.001) higher by 36% and 57%, respectively, compared with control values. Subjects with low HDL-C levels (35 mg/dL). Therefore, we stratified participants according to HDL-C concentrations into low and normal groups. The differences in lipid levels between controls and HDL-C-matched cases substantially decreased; however, the significant differences in HDL subspecies remained. Our research findings support the concept that compared with control subjects, CHD patients not only have HDL deficiency but also have a major rearrangement in the HDL subpopulations with significantly lower alpha(1) and pre-alpha(1-3) (LpA-I) and significantly higher alpha(3) (LpA-I/A-II) particles.
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