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Publication : Vav family Rho guanine nucleotide exchange factors regulate CD36-mediated macrophage foam cell formation.

First Author  Rahaman SO Year  2011
Journal  J Biol Chem Volume  286
Issue  9 Pages  7010-7
PubMed ID  21209086 Mgi Jnum  J:170538
Mgi Id  MGI:4946852 Doi  10.1074/jbc.M110.192450
Citation  Rahaman SO, et al. (2011) Vav family Rho guanine nucleotide exchange factors regulate CD36-mediated macrophage foam cell formation. J Biol Chem 286(9):7010-7
abstractText  Lipid-laden macrophages or 'foam cells' are the primary components of the fatty streak, the earliest atherosclerotic lesion. Although Vav family guanine nucleotide exchange factors impact processes highly relevant to atherogenesis and are involved in pathways common to scavenger receptor CD36 signaling, their role in CD36-dependent macrophage foam cell formation remains unknown. The goal of the present study was to determine the contribution of Vav proteins to CD36-dependent foam cell formation and to identify the mechanisms by which Vavs participate in the process. We found that CD36 contributes to activation of Vav-1, -2, and -3 in aortae from hyperlipidemic mice and that oxidatively modified LDL (oxLDL) induces activation of macrophage Vav in vitro in a CD36 and Src family kinase-dependent manner. CD36-dependent uptake of oxLDL in vitro and foam cell formation in vitro and in vivo was significantly reduced in Vav null macrophages. These studies for the first time link CD36 and Vavs in a signaling pathway required for macrophage foam cell formation.
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