title: Oxidized plasma albumin promotes platelet-endothelial crosstalk and endothelial tissue factor expression.
abstract: Plasma advanced oxidation protein products (AOPPs), a class of pro-inflammatory pathogenic mediators, accumulate in subjects with chronic kidney disease. Whether AOPPs contribute to coagulation abnormalities, which are frequently seen in uremic patients, is unknown. Here we report that AOPPs activate platelets via a CD36-mediated signaling pathway. Activation of signaling pathways by AOPP-platelet interaction resulted in the expression of several platelet activation markers and rapidly induced the expression of CD40 ligand, triggering platelet adhesion to endothelial cells and promoting endothelial tissue factor expression. AOPPs and serum tissue factor levels were considerably increased in end stage renal disease patients on hemodialysis and a significant correlation of AOPPs and serum tissue factor was found. Interestingly, serum levels of AOPPs and tissue factor were substantially lower in stable kidney transplant patients when compared with hemodialysis patients. Given that CD36 is known to transduce the effects of oxidized lipids into platelet hyperactivity, our findings reveal previously unknown pro-thrombotic activities of oxidized plasma albumin via a CD36 dependent pathway.
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
authors.forename: Lisa
authors.initials: L
authors.lastname: Pasterk
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lemesch
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Leber
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Trieb
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
authors.forename: Sanja
authors.initials: S
authors.lastname: Curcic
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Stadlbauer
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
authors.forename: Rufina
authors.initials: R
authors.lastname: Schuligoi
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schicho
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
authors.forename: Akos
authors.initials: A
authors.lastname: Heinemann
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
authors.forename: Gunther
authors.initials: G
authors.lastname: Marsche
mesh_terms: D000293:Adolescent; D000328:Adult; D062107:Advanced Oxidation Protein Products / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D018955:CD36 Antigens / Q000097:blood* / Q000235:genetics; D023201:CD40 Ligand / Q000097:blood / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000235:genetics / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D006435:Renal Dialysis; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism
chemical_list: D062107:Advanced Oxidation Protein Products; D018955:CD36 Antigens; D012709:Serum Albumin; D023201:CD40 Ligand; D013925:Thromboplastin