Research Articles
Composition-function analysis of HDL subpopulations: influence of lipid composition on particle functionality[S]

https://doi.org/10.1194/jlr.RA119000258Get rights and content
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The composition-function relationship of HDL particles and its effects on the mechanisms driving coronary heart disease (CHD) is poorly understood. We tested the hypothesis that the functionality of HDL particles is significantly influenced by their lipid composition. Using a novel 3D-separation method, we isolated five different-sized HDL subpopulations from CHD patients who had low preβ-1 functionality (low-F) (ABCA1-dependent cholesterol-efflux normalized for preβ-1 concentration) and controls who had either low-F or high preβ-1 functionality (high-F). Molecular numbers of apoA-I, apoA-II, and eight major lipid classes were determined in each subpopulation by LC-MS. The average number of lipid molecules decreased from 422 in the large spherical α-1 particles to 57 in the small discoid preβ-1 particles. With decreasing particle size, the relative concentration of free cholesterol (FC) decreased in α-mobility but not in preβ-1 particles. Preβ-1 particles contained more lipids than predicted; 30% of which were neutral lipids (cholesteryl ester and triglyceride), indicating that these particles were mainly remodeled from larger particles not newly synthesized. There were significant correlations between HDL-particle functionality and the concentrations of several lipids. Unexpectedly, the phospholipid:FC ratio was significantly correlated with large-HDL-particle functionality but not with preβ-1 functionality. There was significant positive correlation between particle functionality and total lipids in high-F controls, indicating that the lipid-binding capacity of apoA-I plays a major role in the cholesterol efflux capacity of HDL particles. Functionality and lipid composition of HDL particles are significantly correlated and probably both are influenced by the lipid-binding capacity of apoA-I.

high density lipoprotein
pre-beta
phospholipids
lipid ratios

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This work was supported by National Heart, Lung, and Blood Institute Grant HL117933 and US Federal Government Funds for improved risk assessment of cardiovascular disease. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Centers for Disease Control and Prevention. The authors declare that they have no conflicts of interest with the contents of this article

Abbreviations:

    CE

    cholesteryl ester

    CEC

    cholesterol efflux capacity

    CHD

    coronary heart disease

    FC

    free cholesterol

    high-F

    high preβ-1 functionality

    low-F

    low preβ-1 functionality

    LPC

    lysophosphatidylcholine

    PC

    phosphatidylcholine

    PE

    phosphatidylethanolamine

    PI

    phosphatidylinositol

    PL

    phospholipid

    SR-BI

    scavenger receptor BI

    TG

    triglyceride

[S]

The online version of this article (available at https://www.jlr.org) contains a supplement.

1

K. Niisuke and Z. Kuklenyik contributed equally to this work.