A CD36-dependent signaling cascade is necessary for macrophage foam cell formation. Cell Metab 2006 Sep;4(3):211-21
Date
09/05/2006Pubmed ID
16950138Pubmed Central ID
PMC1855263DOI
10.1016/j.cmet.2006.06.007Scopus ID
2-s2.0-33747859314 (requires institutional sign-in at Scopus site) 425 CitationsAbstract
Accumulation of macrophage foam cells in atherosclerotic blood vessel intima is a critical component of atherogenesis mediated by scavenger receptor-dependent internalization of oxidized LDL. We demonstrated by coimmunoprecipitation and pull-down assays that the macrophage scavenger receptor CD36 associates with a signaling complex containing Lyn and MEKK2. The MAP kinases JNK1 and JNK2 were specifically phosphorylated in macrophages exposed to oxLDL. Using cells isolated from SRA, TLR2, or CD36 null mice, and phospholipid ligands specific for either SRA or CD36, we showed that JNK activation was mediated by CD36. Both foam cell formation and activation of JNK2 in hyperlipidemic mice were diminished in the absence of CD36. Furthermore, inhibition of Src or JNK blocked oxLDL uptake and inhibited foam cell formation in vitro and in vivo. These findings show that a specific CD36-dependent signaling pathway initiated by oxLDL is necessary for foam cell formation and identify potential targets for antiatherosclerosis therapy.
Author List
Rahaman SO, Lennon DJ, Febbraio M, Podrez EA, Hazen SL, 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
Adaptor Proteins, Signal TransducingAnimals
Atherosclerosis
CD36 Antigens
Endothelial Cells
Enzyme Inhibitors
Female
Foam Cells
Hyperlipidemias
Hypolipidemic Agents
Lipoproteins, LDL
MAP Kinase Kinase Kinase 2
Macrophages
Male
Mice
Mice, Knockout
Mitogen-Activated Protein Kinase 9
Oxidation-Reduction
Phosphorylation
Signal Transduction
Toll-Like Receptor 2
src-Family Kinases
