Date of Award

2007

Degree Type

Dissertation

Department

Biological, Geological and Environmental Sciences

First Advisor

Silverstein, Roy

Subject Headings

Blood platelets -- Receptors, Blood platelets -- Activation, Receptor-ligand complexes, CD36, CD36-SNP's, Platelets, Microparticles, Platelet activation, CSD36 on platelets, Electronic books. local

Abstract

CD36 is a scavenger receptor expressed on a wide variety of cells including platelets. It recognizes multiple ligands, yet its function on platelets is incompletely characterized. Endothelial cell-derived microparticles (EMP) have been identified in diseases where platelet activation plays a pivotal role. Because EMP express phosphatidylserine (PS) on their surfaces, a CD36 ligand, we hypothesized that MP may bind to platelets via a PS-CD36 interaction. Human platelets were shown to bind EMP by flow cytometry and fluorescence microscopy. Binding was significantly inhibited by anti-CD36 antibody or using platelets from CD36 null donors. We observed a significant increase in the rate and extent of platelet activation and aggregation to low concentrations of ADP when preincubated with EMP. We thus propose a model where ligands such as EMPs, generated during an acute thrombotic event, could increase the thrombotic response in a CD36 dependent manner. We also showed that CD36 expression levels on platelets were highly variable and correlated well with platelet activation by oxidized LDL. Genotyping with 10 tagged SNPs revealed that the minor alleles of 3 SNPs were significantly associated with expression levels. These data suggest that the variability of CD36 expression on platelets is at least in part genetically determined and together this phenotype-genotype can affect platelet function

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