Blood Journal
Leading the way in experimental and clinical research in hematology

Platelet CD36 surface expression levels affect functional responses to oxidized LDL and are associated with inheritance of specific genetic polymorphisms

  1. Arunima Ghosh1,2,
  2. Gurunathan Murugesan3,
  3. Kan Chen1,4,
  4. Li Zhang5,
  5. Qing Wang6,
  6. Maria Febbraio6,
  7. Rita Marie Anselmo7,
  8. Kandice Marchant3,
  9. John Barnard5, and
  10. Roy L. Silverstein1
  1. 1Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH;
  2. 2Department of Biology, Geology and Environmental Sciences, Cleveland State University, Cleveland, OH;
  3. 3Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH;
  4. 4Program in Cell Biology, Case Western Reserve University, Cleveland, OH; and
  5. Departments of 5Quantitative Health Sciences,
  6. 6Molecular Cardiology, and
  7. 7Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH

Abstract

CD36 modulates platelet function via binding to oxidized LDL (oxLDL), cell-derived microparticles, and thrombospondin-1. We hypothesized that the level of platelet CD36 expression may be associated with inheritance of specific genetic polymorphisms and that this would determine platelet reactivity to oxLDL. Analysis of more than 500 subjects revealed that CD36 expression levels were consistent in individual donors over time but varied widely among donors (200-14 000 molecules per platelet). Platelet aggregometry and flow cytometry in a subset of subjects with various CD36 expression levels revealed a high level of correlation (r2 = 0.87) between platelet activation responses to oxLDL and level of CD36 expression. A genome-wide association study of 374 white subjects from the Cleveland Clinic ASCLOGEN study showed strong associations of single nucleotide polymorphisms in CD36 with platelet surface CD36 expression. Most of these findings were replicated in a smaller subset of 25 black subjects. An innovative gene-based genome-wide scan provided further evidence that single nucleotide polymorphisms in CD36 were strongly associated with CD36 expression. These studies show that CD36 expression on platelets varies widely, correlates with functional responses to oxLDL, and is associated with inheritance of specific CD36 genetic polymorphisms, and suggest that inheritance of specific CD36 polymorphisms could affect thrombotic risk.

  • Submitted February 22, 2011.
  • Accepted March 28, 2011.
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