title: Plasma-advanced oxidation protein products are potent high-density lipoprotein receptor antagonists in vivo.
abstract: Advanced oxidation protein products (AOPPs) are carried by oxidized plasma proteins, especially albumin and accumulate in subjects with renal disease and coronary artery disease. AOPPs represent an excellent novel marker of oxidative stress and their roles in the development of cardiovascular disease might be of great importance. Here, we show that in vitro-generated AOPP-albumin binds with high affinity to the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI). Already an equimolar concentration of AOPP-albumin to HDL blocked HDL association to SR-BI and effectively inhibited SR-BI-mediated cholesterol ester (CE) uptake. Interestingly, albumin extensively modified by advanced glycation end products (AGE-albumin), which is an established SR-BI ligand known to accumulate in renal disease, only weakly interfered with HDL binding to SR-BI. Furthermore, AOPP-albumin administration increased the plasma half-life of [3H]CE-HDL in control mice 1.6-fold (P=0.01) and 8-fold (P=0.0003) in mice infected with adenoviral vectors encoding human SR-BI. Moreover, albumin isolated from hemodialysis patients, but not albumin isolated from healthy controls, markedly inhibited SR-BI-mediated HDL-CE transfer in vitro dependent on the AOPP content of albumin. These results indicate that AOPP-albumin effectively blocks SR-BI in vitro and in vivo. Thus, depressed plasma clearance of HDL-cholesterol may contribute to the abnormal composition of HDL and the high cardiovascular risk observed in patients with chronic renal failure.
authors.affiliation: Center of Theoretical-Clinical Medicine II, Medical University Graz, Universitätsplatz 4, 8010 Graz, Austria. gunther.marsche@meduni-graz.at
authors.forename: Gunther
authors.initials: G
authors.lastname: Marsche
authors.forename: Sasa
authors.initials: S
authors.lastname: Frank
authors.forename: Andelko
authors.initials: A
authors.lastname: Hrzenjak
authors.forename: Michael
authors.initials: M
authors.lastname: Holzer
authors.forename: Sabine
authors.initials: S
authors.lastname: Dirnberger
authors.forename: Christian
authors.initials: C
authors.lastname: Wadsack
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.forename: Akos
authors.initials: A
authors.lastname: Heinemann
authors.forename: Karl
authors.initials: K
authors.lastname: Oettl
mesh_terms: D000418:Albumins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D011485:Protein Binding / Q000235:genetics; D050050:Protein Carbonylation; D012307:Risk Factors; D051122:Scavenger Receptors, Class B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000418:Albumins; D008076:Cholesterol, HDL; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B