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).