title: Uremia alters HDL composition and function.
abstract: Functional impairment of HDL may contribute to the excess cardiovascular mortality experienced by patients with renal disease, but the effect of advanced renal disease on the composition and function of HDL is not well understood. Here, we used mass spectrometry and biochemical analyses to study alterations in the proteome and lipid composition of HDL isolated from patients on maintenance hemodialysis. We identified a significant increase in the amount of acute phase protein serum amyloid A1, albumin, lipoprotein-associated phospholipase A2, and apoC-III composing uremic HDL. Furthermore, uremic HDL contained reduced phospholipid and increased triglyceride and lysophospholipid. With regard to function, these changes impaired the ability of uremic HDL to promote cholesterol efflux from macrophages. In summary, the altered composition of HDL in renal disease seems to inhibit its cardioprotective properties. Assessing HDL composition and function in renal disease may help identify patients at increased risk for cardiovascular disease.
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Holzer
authors.forename: Ruth
authors.initials: R
authors.lastname: Birner-Gruenberger
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.forename: Dalia
authors.initials: D
authors.lastname: El-Gamal
authors.forename: Veronika
authors.initials: V
authors.lastname: Binder
authors.forename: Christian
authors.initials: C
authors.lastname: Wadsack
authors.forename: Akos
authors.initials: A
authors.lastname: Heinemann
authors.forename: Gunther
authors.initials: G
authors.lastname: Marsche
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000378:metabolism; D053305:Apolipoprotein C-III / Q000097:blood; D016022:Case-Control Studies; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002853:Chromatography, Liquid; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism; D020543:Proteome; D006435:Renal Dialysis; D000685:Serum Amyloid A Protein / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014280:Triglycerides / Q000032:analysis; D014511:Uremia / Q000097:blood*
chemical_list: D000418:Albumins; D053305:Apolipoprotein C-III; D008075:Lipoproteins, HDL; D010743:Phospholipids; D020543:Proteome; C521404:SAA1 protein, human; D000685:Serum Amyloid A Protein; D014280:Triglycerides; D002784:Cholesterol