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Updated: Feb 3, 2026
Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
Published on: January 28, 2020
High density lipoprotein proteome is associated with cardiovascular risk factors and atherosclerosis burden as
Scott M Gordon1, Jonathan H Chung2, Martin P Playford2
1Lipoprotein Metabolism Section, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
Insights
The high-density lipoprotein (HDL) proteome, not just HDL cholesterol (HDL-C), offers insights into cardiovascular disease (CVD) risk. HDL-bound proteins better reflect atherosclerosis burden and HDL function than HDL-C levels alone.
Area of Science:
- Cardiovascular Disease Research
- Proteomics
- Biomarker Discovery
Background:
- High-density lipoprotein cholesterol (HDL-C) levels are linked to cardiovascular disease (CVD) risk, but therapies targeting HDL-C have not reduced CVD events.
- This suggests HDL-C levels do not fully represent HDL's atheroprotective function.
Purpose of the Study:
- To investigate the relationship between HDL-bound proteins, atherosclerosis burden, and HDL function.
- To determine if the HDL proteome provides additional information beyond HDL-C for CVD risk assessment.
Main Methods:
- Analyzed the HDL proteome using mass spectrometry in 126 subjects.
- Quantified atherosclerosis burden (calcified and non-calcified plaque) using coronary computed tomography angiography (CCTA).
- Used partial least squares regression to associate HDL proteins with atherosclerosis and cholesterol efflux capacity (CEC).
Main Results:
- Proteins associated with non-calcified plaque (NCB) showed an inverse correlation with CEC, linking HDL function to plaque burden.
- Calcified plaque (CB) burden was associated with a distinct set of HDL proteins.
- Body Mass Index (BMI) significantly influenced HDL proteins more than gender, age, or HDL-C.
Conclusions:
- The HDL proteome contains valuable information not reflected by HDL-C, indicating its potential as a CVD risk biomarker.
- HDL protein composition may guide the development of therapies targeting HDL function for CVD risk reduction.
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.
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