Zhao_2012_Zhonghua.Xin.Xue.Guan.Bing.Za.Zhi_40_248

OBJECTIVE: To observe the effects of soluble epoxide hydrolase inhibitor t-AUCB on foam cell formation and cholesterol efflux in macrophage.
METHODS: Mouse macrophages RAW264.7 were cultured and stimulated with ox-LDL (80 micromol/L) in the absence (group A) or presence of t-AUCB (1, 10, 50, 100 micromol/L, group B) or t-AUCB (100 micromol/L) pretreated with PPARgamma antagonist GW9662 (5 micromol/L, group C). The foam cell was identified by oil red O staining. The cholesterol efflux rates of (3)H-cholesterol in cells were measured by liquid scintillation counter. mRNA and protein expressions of ABCA1 were detected by real-time PCR or Western blot, respectively.
RESULTS: Oil red O staining showed that t-AUCB (100 micromol/L) significantly inhibited foam cell formation which could be significantly reversed by GW9662 (all P < 0.05). t-AUCB dose-dependently increased cholesterol efflux rates in mouse macrophage [(5.91 +/- 0.18)% in group A, (7.03 +/- 0.33)%, (8.05 +/- 0.32)%, (9.04 +/- 0.14)%, (10.06 +/- 0.85)% in 1, 10, 50, 100 micromol/L t-AUCB groups, all P < 0.05 vs. group A], which could be reversed by pretreatment with GW9662 [(6.33 +/- 0.15)% in 100 micromol/L t-AUCB + GW9662 group].t-AUCB also upregulated ABCA1 mRNA and protein expressions in a dose-dependent manner which could be significantly attenuated by pretreatment with GW9662. CONCLUSION: t-AUCB could inhibit foam cell formation by improving cholesterol efflux through activating PPARgamma-ABCA1 pathway in macrophage.