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

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


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Animals
  • Atherosclerosis / diagnostic imaging*
  • Atherosclerosis / metabolism
  • Biomarkers / metabolism
  • Body Mass Index
  • Cardiovascular Diseases / diagnostic imaging*
  • Cardiovascular Diseases / metabolism
  • Cell Line
  • Cholesterol, HDL
  • Computed Tomography Angiography
  • Coronary Angiography
  • Female
  • Humans
  • Lipoproteins, HDL / metabolism*
  • Male
  • Mice
  • Middle Aged
  • Plaque, Atherosclerotic
  • Proteome
  • Regression Analysis
  • Risk Factors


  • Biomarkers
  • Cholesterol, HDL
  • Lipoproteins, HDL
  • Proteome