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Serum Amyloid A in Uremic HDL Promotes Inflammation
Open accessAbstract
Uremia impairs the atheroprotective properties of HDL, but the mechanisms underlying why this occurs are unknown. Here, we observed that HDL isolated from healthy individuals inhibited the production of inflammatory cytokines by peripheral monocytes stimulated with a Toll-like receptor 2 agonist. In contrast, HDL isolated from the majority of patients with ESRD did not show this anti-inflammatory property; many HDL samples even promoted the production of inflammatory cytokines. To investigate this difference, we used shotgun proteomics to identify 49 HDL-associated proteins in a uremia-specific pattern. Proteins enriched in HDL from patients with ESRD (ESRD-HDL) included surfactant protein B (SP-B), apolipoprotein C-II, serum amyloid A (SAA), and α-1-microglobulin/bikunin precursor. In addition, we detected some ESRD-enriched proteins in earlier stages of CKD. We did not detect a difference in oxidation status between HDL isolated from uremic and healthy patients. Regarding function of these uremia-specific proteins, only SAA mimicked ESRD-HDL by promoting inflammatory cytokine production. Furthermore, SAA levels in ESRD-HDL inversely correlated with its anti-inflammatory potency. In conclusion, HDL has anti-inflammatory activities that are defective in uremic patients as a result of specific changes in its molecular composition. These data suggest a potential link between the high levels of inflammation and cardiovascular mortality in uremia.
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“In patients with diabetes mellitus, coronary disease, chronic renal insufficiency, cardiovascular risk factors and disorders, the function of HDL is impaired [9, 61, 70–74].”
From HDL cholesterol: reappraisal of its clinical relevance (2017) · cites this paper as [73]
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Metadata
- Authors
- Weichhart, T., Kopecky, C., Kubicek, M., Haidinger, M., Döller, D., Katholnig, K., Suarna, C., Eller, P., Tölle, M., Gerner, C., Zlabinger, G. J., van der Giet, M., Hörl, W. H., Stocker, R., & Säemann, M. D.
- Affiliations
- Medical University of Vienna (AT)
- The University of Sydney (AU)
- Medical University of Graz (AT)
- Charité – Universitätsmedizin Berlin (DE)
- Comprehensive Cancer Center Vienna (AT)
- Corresponding author
- Weichhart, Thomas
- Kopecky, Chantal
- Haidinger, Michael
- Döller, Dominik
- Katholnig, Karl
- Zlabinger, Gerhard J.
- Hörl, Walter H.
- Säemann, Marcus D.
- ORCID
- Venue
- Journal of the American Society of Nephrology
- Published
- 2012-05
- Volume
- 23
- Issue
- 5
- Pages
- 934-947
- ISSN
- 1046-6673 (ISSN-L)
- PMC
- PMC3338291
- OpenAlex
- W2139976637
- Cited by
- 201
- References
- 81
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 13 · 2021: 18 · 2020: 11 · 2019: 15 · 2018: 17 · 2017: 20 · 2016: 17 · 2015: 22 · 2014: 21 · 2013: 18 · 2012: 6
- FWCI
- 16.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- serum amyloid A, end-stage renal disease, HDL dysfunction, inflammation, inflammatory cytokines, TLR2, monocytes, HDL-associated proteins, surfactant protein B, apolipoprotein C-II, alpha1-microglobulin, HDL oxidation, chronic kidney disease, cardiovascular mortality
- MeSH terms
- Adult, Aged, Serum Amyloid A Protein, Female, Humans, Inflammation, Iron, Kidney Failure, Chronic, Lipoproteins, HDL, Male, Middle Aged, Oxidation-Reduction, Uremia, Pulmonary Surfactant-Associated Protein B, Proteomics
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