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Objective: Oxidized low-density lipoprotein (Ox-LDL) is associated with atherosclerotic events through the modulation of arachidonic acid (AA) metabolism and activation of inflammatory signaling.Cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) mitigate inflammation through nuclear factor-κB (NF-κB).In this study, we explored the effects and mechanisms of exogenous EETs on the ox-LDL-induced inflammation of pulmonary artery endothelial cells (PAECs), which were cultured from rat pulmonary arteries.Methods: The endothelial receptor of lectin-like oxidized low-density lipoprotein (LOX-1), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and E-selectin mRNA and protein levels were determined by qRT-PCR and ELISA.The CYP2J4 mRNA and protein levels were measured by qRT-PCR and Western blot.The protein levels of Erk1/2, p38, Iκ IBα, and p65 were measured by Western blotting.Results: We determined that pre-treatment with 11,12-EET or 14,15-EET attenuated the ox-LDL-induced expression and release of ICAM-1, E-selectin, and MCP-1 in a concentration-dependent manner in a concentration-dependent manner.In addition, the ox-LDL-induced expression of CYP2J4 was upregulated by 11,12-EET and 14,15-EET (1 μM).Furthermore, LOX-1 receptor was downregulated in PAECs treated with EETs.The inflammatory responses evoked by ox-LDL (100 μg/mL) were blocked by pharmacological inhibitors of Erkl/2 mitogen-activated protein kinase (MAPK) (U0126), p38 MAPK (SB203580), and NF-κB (PDTC).In addition, we confirmed that 11,12-EET suppresses the phosphorylation of p38, the degradation of IκBα, and the activation of NF-κB (p65), whereas 14,15-EET can significantly suppress the phosphorylation of p38 and Erk1/2.Conclusion: Our results indicate that EETs exert beneficial effects on ox-LDL-induced inflammation primarily through the inhibition of LOX-1 receptor upregulation, MAPK phosphorylation, and NF-κB activation and through the upregulation of CYP2J4 expression.This study helps focus the current understanding of the contribution of EETs to the regulation of the inflammation of pulmonary vascular endothelial cells.Furthermore, the therapeutic potential of targeting the EET pathway in pulmonary vascular disease will be highlighted.