[Soluble epoxide hydrolase inhibitor t-AUCB ameliorates ox-LDL induced conversion of macrophages into foam cells through activating the PPARγ-ABCA1 pathway].
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 µmol/L) in the absence (group A) or presence of t-AUCB (1, 10, 50, 100 µmol/L, group B) or t-AUCB (100 µmol/L) pretreated with PPARγ antagonist GW9662 (5 µmol/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 µmol/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 µmol/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 µmol/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.


CONCLUSIONS
t-AUCB could inhibit foam cell formation by improving cholesterol efflux through activating PPARγ-ABCA1 pathway in macrophage.
Department of Internal Cardiology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Ting-ting
TT
Zhao
Ran
R
Peng
Li
L
Shen
Xuan
X
Zhao
Dan-yan
DY
Xu
Shui-ping
SP
Zhao
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D005487:Foam Cells / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
C524106:4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001565:Benzoates; D004791:Enzyme Inhibitors; D047495:PPAR gamma; D014508:Urea; D002784:Cholesterol; D004851:Epoxide Hydrolases