TY - JOUR T1 - Atheroprotective Effect of Oleoylethanolamide (OEA) Targeting Oxidized LDL A1 - Fan, Angran A1 - Wu, Xiaofeng A1 - Wu, Huijuan A1 - Li, Long A1 - Huang, Rui A1 - Zhu, Yueyong A1 - Qiu, Yan A1 - Fu, Jin A1 - Ren, Jie A1 - Zhu, Chenggang Y1 - 2014/01/20 N2 - 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. JF - PLOS ONE JA - PLOS ONE VL - 9 IS - 1 UR - https://doi.org/10.1371/journal.pone.0085337 SP - e85337 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pone.0085337 ER -