Cited by 944Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthAtherosclerosis and Cardiovascular Diseases

Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL

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Vaisar, Tomas, Pennathur, Subramaniam, Green, Pattie S., Gharib, Sina A., Hoofnagle, Andrew N., Cheung, Marian C., Byun, Jaeman, Vuletic, Simona +13 more·2007·Journal of Clinical Investigation

Abstract

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 antiinflammatory and antiatherogenic properties.

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Crossref · 10.1172/jci26206

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  • Unlike HDL from healthy subjects, HDL from patients with CHD, kidney disease or diabetes mellitus have no protective vascular effects or may even cause paradoxical harmful effects.

    “Unlike HDL from healthy subjects, HDL from patients with CHD, kidney disease or diabetes mellitus have no protective vascular effects or may even cause paradoxical harmful effects [55, 56, 61, 70, 71, 75, 76].”

    From HDL cholesterol: reappraisal of its clinical relevance (2017) · cites this paper as [56]

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Authors
Vaisar, T., Pennathur, S., Green, P. S., Gharib, S. A., Hoofnagle, A. N., Cheung, M. C., Byun, J., Vuletic, S., Kassim, S., Singh, P., Chea, H., Knopp, R. H., Brunzell, J., Geary, R., Chait, A., Zhao, X.-Q., Elkon, K., Marcovina, S., Ridker, P., Oram, J. F., & Heinecke, J. W.
Affiliations
  • University of Washington (US)
  • Wake Forest University (US)
  • Harvard University (US)
Corresponding author
Heinecke, Jay W.
Venue
Journal of Clinical Investigation
Published
2007-03-01
Volume
117
Issue
3
Pages
746-756
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2083315579
Cited by
942
References
70
Citations by year
2026: 16 · 2025: 20 · 2024: 19 · 2023: 25 · 2022: 36 · 2021: 28 · 2020: 35 · 2019: 36 · 2018: 45 · 2017: 31 · 2016: 51 · 2015: 69 · 2014: 58 · 2013: 81 · 2012: 79
FWCI
79.98
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Washington (P30ES07033)
  • National Institutes of Health (P30ES07033, DK017047)
  • National Heart, Lung, and Blood Institute (HL086798, P01HL030086, HL-078527, K08HL074223, HL-57557, HL074223, R01HL086798, R01HL057557, R01HL078527)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK017047, DK 02456, P01DK002456, P30DK017047)
  • National Institute of Environmental Health Sciences (P30 ES-07033, P30ES007033)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
HDL cholesterol, HDL proteome, complement regulation, serpins, protease inhibition, anti-inflammatory activity, coronary artery disease, HDL3, apolipoprotein E, acute phase proteins, atherosclerosis, cardiovascular disease
MeSH terms
Amino Acid Sequence, Chromatography, Liquid, Complement Activation, Coronary Artery Disease, Humans, Inflammation, Lipoproteins, HDL, Microscopy, Electron, Scanning, Molecular Sequence Data, Peptide Hydrolases, Mass Spectrometry, Proteomics, Lipid Metabolism

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