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Oxidized plasma albumin promotes platelet-endothelial crosstalk and endothelial tissue factor expression
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Oxidized plasma albumin promotes platelet-endothelial crosstalk and endothelial tissue factor expression
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Journal Article
Oxidized plasma albumin promotes platelet-endothelial crosstalk and endothelial tissue factor expression
2016
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adult
/ Advanced Oxidation Protein Products - blood
/ Advanced Oxidation Protein Products - chemistry
/ Advanced Oxidation Protein Products - pharmacology
/ Aged
/ Albumin
/ Blood Platelets - metabolism
/ Endothelial Cells - metabolism
/ Endothelial Cells - pathology
/ Female
/ Humanities and Social Sciences
/ Humans
/ Kidney Failure, Chronic - blood
/ Kidney Failure, Chronic - genetics
/ Kidney Failure, Chronic - pathology
/ Lipids
/ Male
/ Platelet Activation - drug effects
/ Platelet Aggregation - drug effects
/ Science
/ Serum Albumin - pharmacology
/ Tissues
