Platelet CD36 surface expression levels affect functional responses to oxidized LDL and are associated with inheritance of specific genetic polymorphisms. Blood 2011 Jun 09;117(23):6355-66
Date
04/12/2011Pubmed ID
21478428Pubmed Central ID
PMC3122954DOI
10.1182/blood-2011-02-338582Scopus ID
2-s2.0-79959465233 (requires institutional sign-in at Scopus site) 89 CitationsAbstract
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.
Author List
Ghosh A, Murugesan G, Chen K, Zhang L, Wang Q, Febbraio M, Anselmo RM, Marchant K, Barnard J, Silverstein RLAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedBlood Donors
Blood Platelets
CD36 Antigens
Cell-Derived Microparticles
Female
Gene Expression Regulation
Genome-Wide Association Study
Humans
Lipoproteins, LDL
Male
Middle Aged
Polymorphism, Single Nucleotide
Risk Factors
Thrombosis
