BACKGROUND: There is evidence that CD36 promotes foam cell formation through internalizing oxidized LDL (ox-LDL) into macrophages; therefore, it plays a key role in pathogenesis of atherosclerosis. In addition, CD36 expression seems to be mediated by nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ). The aim of the present study was to evaluate and compare the effect of PPAR-γ ligands, eicosapentaenoic acid (EPA) as an anti-atherogenic factor and ox-LDL as an atherogenic factor on CD36 expression. Mechanism of PPAR- γ action and its ligands in CD36 expression were also investigated. METHODS: Raw 264.7 macrophage cell line was treated with ox-LDL (100 and 150 μg protein/LDL) and EPA (100 and 200 μM) for 24 and 48 hours in absence or presence of PPAR-γ inhibitor, T0070907. Quantitative real-time PCR and Western-blotting were used for analysis of gene and protein expression, respectively. RESULTS: Raw 264.7 exposures to ox-LDL and EPA resulted in increased expression of CD36 mRNA and protein; however, mRNA and PPAR-γ protein were not up-regulated significantly. Pre-incubation of cells with T0070907 led to decreased expression of CD36 when treated with ox-LDL and EPA. CONCLUSION: It was confirmed that both EPA and ox-LDL increased CD36 expression but not PPAR-γ, and also co-treatment with PPAR-γ inhibitor decreased CD36 expression. We concluded that up-regulation of CD36 depends on PPAR-γ activation and is not related to increased expression of PPAR-γ. Induction of CD36 by EPA showed that CD36 suppression is not the means by which ω-3 fatty acids (EPA) provide protection against formation of atherosclerotic plaque.
BACKGROUND: There is evidence that CD36 promotes foam cell formation through internalizing oxidized LDL (ox-LDL) into macrophages; therefore, it plays a key role in pathogenesis of atherosclerosis. In addition, CD36 expression seems to be mediated by nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ). The aim of the present study was to evaluate and compare the effect of PPAR-γ ligands, eicosapentaenoic acid (EPA) as an anti-atherogenic factor and ox-LDL as an atherogenic factor on CD36 expression. Mechanism of PPAR- γ action and its ligands in CD36 expression were also investigated. METHODS: Raw 264.7 macrophage cell line was treated with ox-LDL (100 and 150 μg protein/LDL) and EPA (100 and 200 μM) for 24 and 48 hours in absence or presence of PPAR-γ inhibitor, T0070907. Quantitative real-time PCR and Western-blotting were used for analysis of gene and protein expression, respectively. RESULTS: Raw 264.7 exposures to ox-LDL and EPA resulted in increased expression of CD36 mRNA and protein; however, mRNA and PPAR-γ protein were not up-regulated significantly. Pre-incubation of cells with T0070907 led to decreased expression of CD36 when treated with ox-LDL and EPA. CONCLUSION: It was confirmed that both EPA and ox-LDL increased CD36 expression but not PPAR-γ, and also co-treatment with PPAR-γ inhibitor decreased CD36 expression. We concluded that up-regulation of CD36 depends on PPAR-γ activation and is not related to increased expression of PPAR-γ. Induction of CD36 by EPA showed that CD36 suppression is not the means by which ω-3 fatty acids (EPA) provide protection against formation of atherosclerotic plaque.
Authors: M Febbraio; E A Podrez; J D Smith; D P Hajjar; S L Hazen; H F Hoff; K Sharma; R L Silverstein Journal: J Clin Invest Date: 2000-04 Impact factor: 14.808
Authors: H Singh Ahuja; S Liu; D L Crombie; M Boehm; M D Leibowitz; R A Heyman; C Depre; L Nagy; P Tontonoz; P J Davies Journal: Mol Pharmacol Date: 2001-04 Impact factor: 4.436
Authors: K J Moore; E D Rosen; M L Fitzgerald; F Randow; L P Andersson; D Altshuler; D S Milstone; R M Mortensen; B M Spiegelman; M W Freeman Journal: Nat Med Date: 2001-01 Impact factor: 53.440
Authors: Gary Lee; Fabienne Elwood; John McNally; Jennifer Weiszmann; Michelle Lindstrom; Kate Amaral; Motonao Nakamura; Shichang Miao; Ping Cao; R Marc Learned; Jin-Long Chen; Yang Li Journal: J Biol Chem Date: 2002-03-04 Impact factor: 5.157