The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL
Open accessAbstract
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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“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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Cites
A statistical model for identifying proteins by tandem mass spectrometry.
Nesvizhskii, A., Keller, A., Kolker, E., & Aebersold, R. (2003) · Analytical Chemistry · doi:10.1021/ac0341261 · Cited by 4,902
A Model for Random Sampling and Estimation of Relative Protein Abundance in Shotgun Proteomics
Liu, H., Sadygov, R. G., & Yates, J. R. (2004) · Analytical Chemistry · doi:10.1021/ac0498563 · Cited by 2,533
Direct analysis of protein complexes using mass spectrometry
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Identifying biological themes within lists of genes with EASE
Hosack, D. A., Dennis, G., Sherman, B. T., Lane, H. C., & Lempicki, R. A. (2003) · Genome biology · doi:10.1186/gb-2003-4-10-r70 · Cited by 1,961
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Hoyert, D. L., Kung, H.-C., & Smith, B. L. (2005) · PubMed · Cited by 1,649
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Albert, M. A., Danielson, E., Rifai, N., Ridker, P. M., & for the PRINCE Investigators (2001) · JAMA · doi:10.1001/jama.286.1.64 · Cited by 1,644
Self-citationHigh-Density Lipoprotein — The Clinical Implications of Recent Studies
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Antiinflammatory Properties of HDL
Barter, P. J., Nicholls, S., Rye, K.-A., Anantharamaiah, G. M., Navab, M., & Fogelman, A. M. (2004) · Circulation Research · doi:10.1161/01.res.0000146094.59640.13 · Cited by 1,394
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Progress and challenges in translating the biology of atherosclerosis
Libby, P., Ridker, P. M., & Hansson, G. K. (2011) · Nature · doi:10.1038/nature10146 · Cited by 4,010
“HDL particles associate with dozens of proteins, many with biological activities that have relevance to atherogenesi”
BackgroundSelf-citationLundqvist, M., Stigler, J., Elia, G., Lynch, I., Cedervall, T., & Dawson, K. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805135105 · Cited by 3,109
“The 50-nm amine-modified particles have the highest number of detected apolipoproteins, 9 of the 10 identified being associated with HDL, suggesting that 50-nm amine-modified particles associate with HDL. Apolipoprotein B-100 (the major protein in VLDL and LDL particles, but not HDL) (16) is associated with all 50-nm…”
BackgroundInfluentialCholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis
Khera, A. V., Cuchel, M., de la Llera-Moya, M., Rodrigues, A., Burke, M. F., Jafri, K., French, B. C., Phillips, J. A., Mucksavage, M. L., Wilensky, R. L., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1001689 · Cited by 1,943
Cholesterol Efflux and Atheroprotection: Advancing the Concept of Reverse Cholesterol Transport
Rosenson, R. S., Brewer, H. B., Davidson, W. S., Fayad, Z. A., Fuster, V., Goldstein, J., Hellerstein, M., Jiang, X.-C., Phillips, M. C., Rader, D. J., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.066589 · Cited by 953
“This suggests that the term “HDL” refers to a constellation of distinct protein and lipid constructs that share a similar density (20,21), but may vary widely in function (22), as originally suggested by Alaupovic and colleagues (23).”
BackgroundTenzer, S., Docter, D., Rosfa, S., Wlodarski, A., Kuharev, J., Rekik, A., Knauer, S. K., Bantz, C., Nawroth, T., Bier, C., et al. (2011) · ACS Nano · doi:10.1021/nn201950e · Cited by 873
“A functionally diverse group of plasma proteins that we found highly enriched in the corona of the SiNPs are apolipoproteins, involved in lipid and cholesterol transport andmetabolism.(39,40) Several individualmembers of the apolipoprotein family as well as lipids have also been detected on other nanomaterials,(12,18,…”
Background
Metadata
- 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.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2007-03-01
- Volume
- 117
- Issue
- 3
- Pages
- 746-756
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1804352
- 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
- bronze
- doi.org
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › 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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