A Pro-Atherogenic HDL Profile in Coronary Heart Disease Patients: An iTRAQ Labelling-Based Proteomic Approach |
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| Authors: | Li-rong Yan Dong-xue Wang Hong Liu Xiao-xing Zhang Hui Zhao Lu Hua Ping Xu Yi-shi Li |
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| Affiliation: | 1. Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, State Key Laboratory of Cardiovascular Diseases, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; 2. Department of Cardiology, Wuxi People'' Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.; University of Louisville, United States of America, |
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| 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. |
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