Mechanisms of cell signaling by the scavenger receptor CD36: implications in atherosclerosis and thrombosis.
CD36 is a multifunctional membrane receptor present on mononuclear phagocytes, platelets, and other cells that serves as a scavenger receptor for oxidized phospholipids, apoptotic cells and certain microbial pathogens. On macrophages, CD36 interaction with oxidized LDL (oxLDL) triggers a signaling response that is pro-inflammatory and pro-atherogenic. The signaling pathway involves activation of src-family kinases, MAP kinases, and Vav family guanine nucleotide exchange factors and results in ligand internalization, foam cell formation and inhibition of migration. On platelets, CD36 interaction with oxLDL and cell-derived microparticles transduces intracellular signals that render them more reactive to low concentrations of classical agonists. In vitro studies and in vivo experiments in CD36 null mice have revealed an important mechanistic role for CD36 in atherosclerosis and thrombosis. Identification of the precise CD36 signaling pathways in specific cells elicited in response to specific ligands may yield novel targets for drug development in athero-thrombotic disorders.
Silverstein
Roy L
RL
Department of Cell Biology, Lerner Research Institute, NC10, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA. silverr2@ccf.org
Li
Wei
W
Park
Young Mi
YM
Rahaman
S Ohidar
SO
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D001792:Blood Platelets / Q000502:physiology; D018955:CD36 Antigens / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D055252:Cell-Derived Microparticles / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology; D005487:Foam Cells / Q000473:pathology / Q000502:physiology; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D058226:Plaque, Atherosclerotic / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D013927:Thrombosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein