title: Serum amyloid A in uremic HDL promotes inflammation.
abstract: 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.
authors.affiliation: Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria. thomas.weichhart@meduniwien.ac.at
authors.forename: Thomas
authors.initials: T
authors.lastname: Weichhart
authors.forename: Chantal
authors.initials: C
authors.lastname: Kopecky
authors.forename: Markus
authors.initials: M
authors.lastname: Kubicek
authors.forename: Michael
authors.initials: M
authors.lastname: Haidinger
authors.forename: Dominik
authors.initials: D
authors.lastname: Döller
authors.forename: Karl
authors.initials: K
authors.lastname: Katholnig
authors.forename: Cacang
authors.initials: C
authors.lastname: Suarna
authors.forename: Philipp
authors.initials: P
authors.lastname: Eller
authors.forename: Markus
authors.initials: M
authors.lastname: Tölle
authors.forename: Christopher
authors.initials: C
authors.lastname: Gerner
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
authors.forename: Markus
authors.initials: M
authors.lastname: van der Giet
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Roland
authors.initials: R
authors.lastname: Stocker
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007501:Iron / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood; D008075:Lipoproteins, HDL / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D040901:Proteomics; D037701:Pulmonary Surfactant-Associated Protein B / Q000097:blood; D000685:Serum Amyloid A Protein / Q000502:physiology*; D014511:Uremia / Q000097:blood*
chemical_list: D008075:Lipoproteins, HDL; D037701:Pulmonary Surfactant-Associated Protein B; D000685:Serum Amyloid A Protein; D007501:Iron