Vav family Rho guanine nucleotide exchange factors regulate CD36-mediated macrophage foam cell formation. J Biol Chem 2011 Mar 04;286(9):7010-7
Date
01/07/2011Pubmed ID
21209086Pubmed Central ID
PMC3044957DOI
10.1074/jbc.M110.192450Scopus ID
2-s2.0-79953212244 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
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.
Author List
Rahaman SO, Swat W, Febbraio M, 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
AnimalsAtherosclerosis
CD36 Antigens
Cells, Cultured
Foam Cells
Hyperlipidemias
Lipoproteins, LDL
MAP Kinase Signaling System
Macrophages, Peritoneal
Mice
Mice, Mutant Strains
Proto-Oncogene Proteins c-vav
Vasculitis
