期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 117, 期 3, 页码 746-756出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI26206
关键词
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资金
- NHLBI NIH HHS [R01 HL078527, HL57557, P01 HL030086, P01HL030086, K08 HL074223, HL074223, HL086798, R01 HL057557, HL078527, R01 HL086798] Funding Source: Medline
- NIDDK NIH HHS [DK017047, P30 DK017047, P01 DK002456, DK02456, P30DK017047] Funding Source: Medline
- NIEHS NIH HHS [P30ES07033, P30 ES007033] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL078527, R01HL086798, R01HL057557, P01HL030086, K08HL074223] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK017047] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES007033] Funding Source: NIH RePORTER
HDL lowers the risk for atherosclerotic cardiovascular disease by promoting cholesterol efflux from macrophage foam cells. However, other antiatherosclerotic properties of HDL are poorly understood. To test the hypothesis that the lipoprotein carries proteins that might have novel cardioprotective activities, we used shotgun proteomics to investigate the composition of HDL isolated from healthy subjects and subjects with coronary artery disease (CAD). Unexpectedly, our analytical strategy identified multiple complement-regulatory proteins and a diverse array of distinct serpins with serine-type endopeptidase inhibitor activity. Many acute-phase response proteins were also detected, supporting the proposal that HDL is of central importance in inflammation. Mass spectrometry and biochemical analyses demonstrated that HDL3 from subjects with CAD was selectively enriched in apoE, raising the possibility that HDL carries a unique cargo of proteins in humans with clinically significant cardiovascular disease. Collectively, our observations suggest that HDL plays previously unsuspected roles in regulating the complement system and protecting tissue from proteolysis and that the protein cargo of HDL contributes to its and inflammatory and antiatherogenic properties.
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