The HDL proteome in acute coronary syndromes shifts to an inflammatory profile

Khalid Alwaili, Dana Bailey, Zuhier Awan, Swneke D. Bailey, Isabelle Ruel, Anouar Hafiane, Larbi Krimbou, Sylvie Laboissiere, Jacques Genest

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134 Citations (Scopus)

Abstract

Inflammation is a major factor underlying acute coronary syndromes (ACS). HDL particles may be remodeled, becoming functionally defective, under the inflammatory conditions seen in ACS. Shotgun proteomics was used to monitor changes in the HDL proteome between male age-matched control, stable CAD, and ACS subjects (n = 10/group). HDL was isolated by ultracentrifugation and separated by 1D-gel followed by LC-MS/MS. We identified 67 HDL-associated proteins, 20 of which validated recently identified proteins including vitronectin and complement C4B, and 5 of which were novel. Using gene ontology analysis, we found that the HDL-proteome consisted of proteins involved in cholesterol homeostasis (~ 50%), with significant contributions by proteins involved in lipid binding, antioxidant, acute-phase response, immune response, and endopeptidase/protease inhibition. Importantly, levels of apoA-IV were significantly reduced in ACS patients, whereas levels of serum amyloid A (SAA) and complement C3 (C3) were significantly increased (spectral counting; t-test p ≤ 0.05), as confirmed by immunoblot or ELISA. Despite differences in protein composition, ABCA1, ABCG1, and SR-BI mediated cholesterol efflux assays did not indicate that HDL from ACS patients is functionally deficient as compared to controls, when corrected for apoA-I mass. Our results support that the HDL proteome differs between control, CAD and ACS patients. Increased abundance of SAA, C3, and other inflammatory proteins in HDL from ACS patients suggests that HDL reflects a shift to an inflammatory profile which, in turn, might alter the protective effects of HDL on the atherosclerotic plaque. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).

Original languageEnglish
Pages (from-to)405-415
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1821
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Acute coronary syndrome
  • Atherosclerosis
  • High-density lipoprotein
  • Lipid
  • Proteomics

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Alwaili, K., Bailey, D., Awan, Z., Bailey, S. D., Ruel, I., Hafiane, A., Krimbou, L., Laboissiere, S., & Genest, J. (2012). The HDL proteome in acute coronary syndromes shifts to an inflammatory profile. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1821(3), 405-415. https://doi.org/10.1016/j.bbalip.2011.07.013