title: Platelet CD36 surface expression levels affect functional responses to oxidized LDL and are associated with inheritance of specific genetic polymorphisms.
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.
authors.affiliation: Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Arunima
authors.initials: A
authors.lastname: Ghosh
authors.forename: Gurunathan
authors.initials: G
authors.lastname: Murugesan
authors.forename: Kan
authors.initials: K
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Maria
authors.initials: M
authors.lastname: Febbraio
authors.forename: Rita Marie
authors.initials: RM
authors.lastname: Anselmo
authors.forename: Kandice
authors.initials: K
authors.lastname: Marchant
authors.forename: John
authors.initials: J
authors.lastname: Barnard
authors.forename: Roy L
authors.initials: RL
authors.lastname: Silverstein
mesh_terms: D000368:Aged; D001782:Blood Donors; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics; D055252:Cell-Derived Microparticles / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein