A Pro-Atherogenic HDL Profile in Coronary Heart Disease Patients: An iTRAQ Labelling-Based Proteomic Approach

Abstract

ObjectivesThis study aims to compare the protein composition of high-density lipoprotein (HDL) particles in coronary heart disease (CHD) patients and controls by proteomic methods.BackgroundHDL has been reported to exert pro-atherogenic properties in CHD patients. Accumulating evidence indicates that HDL composition, rather than the HDL-C level, determines its functions. The changes in HDL composition involved in the conversion of anti-atherogenic to pro-atherogenic properties in CHD patients are currently unknown.Methods and ResultsiTRAQ combined with nanoLC-MS/MS was performed to obtain a differential expression profile of the HDL pooled samples of the male age-matched CHD patients and controls (n = 10/group). Of the 196 proteins identified in the examined HDL, 12 were differentially expressed between the CHD patients and the controls, including five up-regulated proteins and seven down-regulated proteins. Using GO analysis, we determined that the up-regulated proteins were mostly involved in inflammatory reactions, displaying a potential pro-atherogenic profile. In contrast, the down-regulated proteins were mostly involved in lipid metabolism processes, displaying anti-atherogenic properties. To confirm the proteomic results, serum amyloid A (SAA) and apoC-I were selected and quantified by ELISA, in the same population as the proteomic analysis, as well as another independent population (n = 120/group). Consistent with the proteomic results, the amount of SAA was significantly increased, and apoC-I was significantly decreased in the HDL particles of CHD patients compared with those of controls (P<0.05).ConclusionsOur study shows that the HDL proteome changes to a pro-atherogenic profile in CHD patients, which might compromise the protective effects of HDL. Proteomic analysis of HDL composition may provide more relevant information regarding their functional properties than steady-state HDL-C levels.

Quantifying HDL proteins by mass spectrometry: how many proteins are there and what are their functions?

“…A plethora of recent papers has documented changes in the HDL proteome in disorders ranging from CVD and rheumatoid arthritis to diabetes and metabolic syndrome [74–81]. Many of these studies have centered on mechanistic implications of the observed changes in the HDL proteome.…”

Proteome Dynamics Reveals Pro-Inflammatory Remodeling of Plasma Proteome in a Mouse Model of NAFLD

“…15–18 Importantly, several plasma protein biomarkers of NAFLD and CVD have been identified. 19–21 Although the static measurements of protein abundance are important, they do not allow an understanding of the mechanism for these changes.…”

SAA: a link between cholesterol efflux capacity and inflammation?

“…In another study, HDL isolated from CVD patient plasma identifi ed 196 proteins associated with HDL particles, of which four showed increased expression in CVD patients, whereas a further seven proteins were decreased compared with normal controls ( 38 ). Using MS, and with verifi cation by ELISA, SAA showed a highly signifi cant increase in patient samples, whereas apoC-I levels showed a signifi cant decrease compared with controls.…”