Role of CD36, the macrophage class B scavenger receptor, in atherosclerosis.
Recent work in the field of atherosclerosis has greatly expanded our knowledge of the pathogenesis of this disease. Scavenger receptors, including CD36, are thought to be most important early in the disease progression during macrophage uptake of modified LDL and foam cell formation. Genetically engineered murine models have been used to elucidate the contribution of the different scavenger receptors, to identify specific ligands related to LDL modifications, and to assess the possible therapeutic ramifications of targeting scavenger receptors. We have demonstrated a major role for CD36 in macrophage foam cell development and subsequent lesion development in vivo. Absence of CD36 in an atherogenic Apo E null background resulted in a 70% decrease in total lesion area in Western diet-fed mice. We have also made significant progress in our understanding of the regulation of expression of CD36 and have demonstrated that OxLDL can stimulate its own uptake by induction of CD36 gene expression. The mechanism by which OxLDL upregulates CD36 involves activation of the transcription factor, PPAR-gamma.
Nicholson
A C
AC
Center of Vascular Biology, Cornell University Medical College, New York, New York 10021, USA.
Han
J
J
Febbraio
M
M
Silversterin
R L
RL
Hajjar
D P
DP
D001161:Arteriosclerosis / Q000503:physiopathology*; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology*; D018450:Disease Progression; D005487:Foam Cells / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D008565:Membrane Proteins; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013755:Tetradecanoylphorbol Acetate; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014157:Transcription Factors; C099252:oxidized low density lipoprotein; D013755:Tetradecanoylphorbol Acetate