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Atherosclerosis. 2018 Nov;278:278-285. doi: 10.1016/j.atherosclerosis.2018.09.032. Epub 2018 Sep 25.

High density lipoprotein proteome is associated with cardiovascular risk factors and atherosclerosis burden as evaluated by coronary CT angiography.

Author information

1
Lipoprotein Metabolism Section, National Heart, Lung and Blood Institute, Bethesda, MD, USA. Electronic address: scott.gordon@uky.edu.
2
Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
3
Lipoprotein Metabolism Section, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
4
Bioinformatics and Computational Biology Core Facility, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
5
Advanced Cardiovascular Imaging Laboratory, National Heart, Lung and Blood Institute, Bethesda, MD, USA.

Abstract

BACKGROUND AND AIMS:

High density lipoprotein cholesterol (HDL-C) is associated with risk of cardiovascular disease (CVD); however, therapeutic manipulations of HDL-C have failed to reduce CVD events. This suggests that HDL-C and the atheroprotective capacity of HDL are not directly linked. The goal of this study was to evaluate the relationships between HDL-bound proteins and measures of atherosclerosis burden and HDL function.

METHODS:

The HDL proteome was analyzed using mass spectrometry in 126 human subjects, who had undergone coronary computed tomography angiography (CCTA) to quantify calcified (CB) and non-calcified (NCB) atherosclerosis burden. Partial least squares regression analysis was used to evaluate associations between HDL-bound proteins and CB, NCB, or cholesterol efflux capacity (CEC).

RESULTS:

Significant overlap was found among proteins associated with NCB and CEC. Proteins that were associated with NCB displayed an inverse relationship with CEC, supporting a link between this protective function of HDL and clinical plaque burden. CB was associated with a set of proteins mostly distinct from NCB and CEC. When CVD risk factors were evaluated, BMI had a stronger influence on important HDL proteins than gender, age, or HDL-C. Most HDL proteins associated with function or atherosclerosis burden were not significantly correlated with HDL-C.

CONCLUSIONS:

These findings indicate that the HDL proteome contains information not captured by HDL- C and, therefore, has potential for future development as a biomarker for CVD risk. Additionally, the proteome effects detected in this study may provide HDL compositional goals for evaluating new and existing HDL-modification therapies.

KEYWORDS:

Atherosclerosis; Cholesterol efflux; Computed tomography angiography; High density lipoprotein; Proteomics

PMID:
30347343
PMCID:
PMC6263790
[Available on 2019-11-01]
DOI:
10.1016/j.atherosclerosis.2018.09.032

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