Atheroprotective effect of oleoylethanolamide (OEA) targeting oxidized LDL.
Dietary fat-derived lipid oleoylethanolamide (OEA) has shown to modulate lipid metabolism through a peroxisome proliferator-activated receptor-alpha (PPAR-α)-mediated mechanism. In our study, we further demonstrated that OEA, as an atheroprotective agent, modulated the atherosclerotic plaques development. In vitro studies showed that OEA antagonized oxidized LDL (ox-LDL)-induced vascular endothelial cell proliferation and vascular smooth muscle cell migration, and suppressed lipopolysaccharide (LPS)-induced LDL modification and inflammation. In vivo studies, atherosclerosis animals were established using balloon-aortic denudation (BAD) rats and ApoE(-/-) mice fed with high-caloric diet (HCD) for 17 or 14 weeks respectively, and atherosclerotic plaques were evaluated by oil red staining. The administration of OEA (5 mg/kg/day, intraperitoneal injection, i.p.) prevented or attenuated the formation of atherosclerotic plaques in HCD-BAD rats or HCD-ApoE(-/-) mice. Gene expression analysis of vessel tissues from these animals showed that OEA induced the mRNA expressions of PPAR-α and downregulated the expression of M-CFS, an atherosclerotic marker, and genes involved in oxidation and inflammation, including iNOS, COX-2, TNF-α and IL-6. Collectively, our results suggested that OEA exerted a pharmacological effect on modulating atherosclerotic plaque formation through the inhibition of LDL modification in vascular system and therefore be a potential candidate for anti-atherosclerosis drug.
Department of Medical Science, Medical College, Xiamen University, Xiamen, Fujian, China.
Angran
A
Fan
Department of Medical Science, Medical College, Xiamen University, Xiamen, Fujian, China.
Xiaofeng
X
Wu
Department of Medical Science, Medical College, Xiamen University, Xiamen, Fujian, China.
Huijuan
H
Wu
Department of Medical Science, Medical College, Xiamen University, Xiamen, Fujian, China.
Long
L
Li
Department of Medical Science, Medical College, Xiamen University, Xiamen, Fujian, China.
Rui
R
Huang
Division of Liver Disease, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Yueyong
Y
Zhu
Department of Medical Science, Medical College, Xiamen University, Xiamen, Fujian, China.
Yan
Y
Qiu
Department of Medical Science, Medical College, Xiamen University, Xiamen, Fujian, China.
Jin
J
Fu
Department of Medical Science, Medical College, Xiamen University, Xiamen, Fujian, China.
Jie
J
Ren
School of Life Sciences, Fudan University, Shanghai, China.
Chenggang
C
Zhu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000188:drug therapy; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D063388:Endocannabinoids; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D009829:Oleic Acids / Q000627:therapeutic use*; D047493:PPAR alpha / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
D063388:Endocannabinoids; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D047493:PPAR alpha; C099252:oxidized low density lipoprotein; C488250:oleoylethanolamide