%0 Journal Article
%T Atheroprotective Effect of Oleoylethanolamide (OEA) Targeting Oxidized LDL
%A Angran Fan
%A Xiaofeng Wu
%A Huijuan Wu
%A Long Li
%A Rui Huang
%A Yueyong Zhu
%A Yan Qiu
%A Jin Fu
%A Jie Ren
%A Chenggang Zhu
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0085337
%X Dietary fat-derived lipid oleoylethanolamide (OEA) has shown to modulate lipid metabolism through a peroxisome proliferator-activated receptor-alpha (PPAR-¦Á)-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-¦Á and downregulated the expression of M-CFS, an atherosclerotic marker, and genes involved in oxidation and inflammation, including iNOS, COX-2, TNF-¦Á 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0085337