{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:54:35Z","timestamp":1791665675390,"version":"4.3.4"},"reference-count":165,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81790624"],"award-info":[{"award-number":["81790624"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900341"],"award-info":[{"award-number":["81900341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2020YQ10"],"award-info":[{"award-number":["2020YQ10"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tongji Hospital (HUST) Foundation for Excellent Young Scientist","award":["81790624"],"award-info":[{"award-number":["81790624"]}]},{"name":"Tongji Hospital (HUST) Foundation for Excellent Young Scientist","award":["81900341"],"award-info":[{"award-number":["81900341"]}]},{"name":"Tongji Hospital (HUST) Foundation for Excellent Young Scientist","award":["2020YQ10"],"award-info":[{"award-number":["2020YQ10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Inflammation plays a crucial role in the initiation and development of a wide range of systemic illnesses. Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid (AA) metabolized by CYP450 epoxygenase (CYP450) and are subsequently hydrolyzed by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs), which are merely biologically active. EETs possess a wide range of established protective effects on many systems of which anti-inflammatory actions have gained great interest. EETs attenuate vascular inflammation and remodeling by inhibiting activation of endothelial cells and reducing cross-talk between inflammatory cells and blood vessels. EETs also process direct and indirect anti-inflammatory properties in the myocardium and therefore alleviate inflammatory cardiomyopathy and cardiac remodeling. Moreover, emerging studies show the substantial roles of EETs in relieving inflammation under other pathophysiological environments, such as diabetes, sepsis, lung injuries, neurodegenerative disease, hepatic diseases, kidney injury, and arthritis. Furthermore, pharmacological manipulations of the AA-CYP450-EETs-sEH pathway have demonstrated a contribution to the alleviation of numerous inflammatory diseases, which highlight a therapeutic potential of drugs targeting this pathway. This review summarizes the progress of AA-CYP450-EETs-sEH pathway in regulation of inflammation under different pathological conditions and discusses the existing challenges and future direction of this research field.<\/jats:p>","DOI":"10.3390\/molecules27123873","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T05:25:11Z","timestamp":1655443511000},"page":"3873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["CYP450 Epoxygenase Metabolites, Epoxyeicosatrienoic Acids, as Novel Anti-Inflammatory Mediators"],"prefix":"10.3390","volume":"27","author":[{"given":"Zeqi","family":"Shi","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiological Disorders, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuowen","family":"He","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiological Disorders, Wuhan 430030, China"},{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiological Disorders, Wuhan 430030, China"},{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1056\/NEJM199902113400607","article-title":"Acute-phase proteins and other systemic responses to inflammation","volume":"340","author":"Gabay","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.pharmthera.2014.05.011","article-title":"Human cytochrome P450 epoxygenases: Variability in expression and role in inflammation-related disorders","volume":"144","author":"Shahabi","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41392-020-00443-w","article-title":"Metabolism pathways of arachidonic acids: Mechanisms and potential therapeutic targets","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1056\/NEJMp048288","article-title":"Coxibs and cardiovascular disease","volume":"351","author":"Fitzgerald","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1172\/JCI27291","article-title":"Biological basis for the cardiovascular consequences of COX-2 inhibition: Therapeutic challenges and opportunities","volume":"116","author":"Grosser","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/med.20071","article-title":"Cysteinyl-leukotrienes and their receptors in asthma and other inflammatory diseases: Critical update and emerging trends","volume":"27","author":"Capra","year":"2007","journal-title":"Med. Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S213","DOI":"10.2223\/JPED.1553","article-title":"Antileukotrienes in the treatment of asthma and allergic rhinitis","volume":"82","author":"Ribeiro","year":"2006","journal-title":"J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1073\/pnas.79.3.767","article-title":"Cytochrome P-450-dependent oxygenation of arachidonic acid to hydroxyicosatetraenoic acids","volume":"79","author":"Capdevila","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/nrd2875","article-title":"Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases","volume":"8","author":"Imig","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"36059","DOI":"10.1074\/jbc.R100030200","article-title":"Epoxygenase pathways of arachidonic acid metabolism","volume":"276","author":"Zeldin","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1146\/annurev-pharmtox-011112-140244","article-title":"Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health","volume":"53","author":"Morisseau","year":"2013","journal-title":"Annu. Rev. Pharm. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plipres.2004.10.001","article-title":"Epoxide hydrolases: Their roles and interactions with lipid metabolism","volume":"44","author":"Newman","year":"2005","journal-title":"Prog. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3109\/03602532.2013.837916","article-title":"Influence of inflammation on cardiovascular protective effects of cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids","volume":"46","author":"Shahabi","year":"2014","journal-title":"Drug Metab. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.addr.2011.03.006","article-title":"The roles of CYP450 epoxygenases and metabolites, epoxyeicosatrienoic acids, in cardiovascular and malignant diseases","volume":"63","author":"Xu","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1194\/jlr.M036533","article-title":"CYP2J2 overexpression increases EETs and protects against angiotensin II-induced abdominal aortic aneurysm in mice","volume":"54","author":"Cai","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1002\/jcp.24939","article-title":"Epoxyeicosatrienoic acids regulate macrophage polarization and prevent LPS-induced cardiac dysfunction","volume":"230","author":"Dai","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1194\/jlr.M074229","article-title":"CYP2J2 metabolites, epoxyeicosatrienoic acids, attenuate Ang II-induced cardiac fibrotic response by targeting G\u03b112\/13","volume":"58","author":"He","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e13297","DOI":"10.1111\/apha.13297","article-title":"A synthetic epoxyeicosatrienoic acid analogue prevents the initiation of ischemic acute kidney injury","volume":"227","author":"Hoff","year":"2019","journal-title":"Acta Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.biochi.2019.01.020","article-title":"Role of epoxy-fatty acids and epoxide hydrolases in the pathology of neuro-inflammation","volume":"159","author":"Kodani","year":"2019","journal-title":"Biochimie"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.3945\/an.116.012245","article-title":"The Role of Cytochrome P450 Epoxygenases, Soluble Epoxide Hydrolase, and Epoxyeicosatrienoic Acids in Metabolic Diseases","volume":"7","author":"Xu","year":"2016","journal-title":"Adv. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1194\/jlr.R900004-JLR200","article-title":"Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology","volume":"50","author":"Buczynski","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1126\/science.294.5548.1871","article-title":"Prostaglandins and leukotrienes: Advances in eicosanoid biology","volume":"294","author":"Funk","year":"2001","journal-title":"Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/cvr\/cvn346","article-title":"Eicosanoid signalling pathways in the heart","volume":"82","author":"Jenkins","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev.pharmtox.45.120403.100045","article-title":"Regulation and inhibition of arachidonic acid omega-hydroxylases and 20-HETE formation","volume":"45","author":"Kroetz","year":"2005","journal-title":"Annu. Rev. Pharm. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.bbagen.2004.11.018","article-title":"Cytochrome P450 expression and catalytic activity in coronary arteries and liver of cattle","volume":"1722","author":"Grasso","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/46816","article-title":"Cytochrome P450 2C is an EDHF synthase in coronary arteries","volume":"401","author":"Fisslthaler","year":"1999","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1126\/science.285.5431.1276","article-title":"Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids","volume":"285","author":"Node","year":"1999","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0005-2760(95)00216-2","article-title":"Synthesis of hydroxyeicosatetraenoic (HETEs) and epoxyeicosatrienoic acids (EETs) by cultured bovine coronary artery endothelial cells","volume":"1299","author":"Rosolowsky","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4764","DOI":"10.1074\/jbc.274.8.4764","article-title":"Transfection of an active cytochrome P450 arachidonic acid epoxygenase indicates that 14,15-epoxyeicosatrienoic acid functions as an intracellular second messenger in response to epidermal growth factor","volume":"274","author":"Chen","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1124\/mol.51.6.931","article-title":"CYP2J subfamily cytochrome P450s in the gastrointestinal tract: Expression, localization, and potential functional significance","volume":"51","author":"Zeldin","year":"1997","journal-title":"Mol. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1210\/endo.138.3.4970","article-title":"Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas","volume":"138","author":"Zeldin","year":"1997","journal-title":"Endocrinology"},{"key":"ref_32","first-page":"1111","article-title":"CYP2J subfamily P450s in the lung: Expression, localization, and potential functional significance","volume":"50","author":"Zeldin","year":"1996","journal-title":"Mol. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12551","DOI":"10.1074\/jbc.272.19.12551","article-title":"Molecular cloning, expression, and functional significance of a cytochrome P450 highly expressed in rat heart myocytes","volume":"272","author":"Wu","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.pharmthera.2017.06.006","article-title":"Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases","volume":"180","author":"Wagner","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1161\/01.CIR.93.5.841","article-title":"Report of the 1995 World Health Organization\/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies","volume":"93","author":"Richardson","year":"1996","journal-title":"Circulation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s11427-018-9501-9","article-title":"A life support-based comprehensive treatment regimen dramatically lowers the in-hospital mortality of patients with fulminant myocarditis: A multiple center study","volume":"62","author":"Li","year":"2019","journal-title":"Sci. China. Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1194\/jlr.M017319","article-title":"Epoxyeicosatrienoic acids protect rat hearts against tumor necrosis factor-alpha-induced injury","volume":"53","author":"Zhao","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"H37","DOI":"10.1152\/ajpheart.00983.2008","article-title":"Overexpression of CYP2J2 provides protection against doxorubicin-induced cardiotoxicity","volume":"297","author":"Zhang","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.freeradbiomed.2018.02.009","article-title":"CYP2J2-derived EETs attenuated ethanol-induced myocardial dysfunction through inducing autophagy and reducing apoptosis","volume":"117","author":"Zhou","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.yjmcc.2020.12.013","article-title":"Soluble epoxide hydrolase deficiency attenuates lipotoxic cardiomyopathy via upregulation of AMPK-mTORC mediated autophagy","volume":"154","author":"Wang","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0735-1097(99)00630-0","article-title":"Cardiac remodeling\u2014Concepts and clinical implications: A consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling","volume":"35","author":"Cohn","year":"2000","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nri3800","article-title":"Role of innate and adaptive immune mechanisms in cardiac injury and repair","volume":"15","author":"Epelman","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1093\/cvr\/cvz164","article-title":"Chanzyme TRPM7 protects against cardiovascular inflammation and fibrosis","volume":"116","author":"Rios","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/cvr\/cvv018","article-title":"Cardiomyocyte-specific expression of CYP2J2 prevents development of cardiac remodelling induced by angiotensin II","volume":"105","author":"He","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1111\/acel.12507","article-title":"CYP2J2 and its metabolites (epoxyeicosatrienoic acids) attenuate cardiac hypertrophy by activating AMPK\u03b12 and enhancing nuclear translocation of Akt1","volume":"15","author":"Wang","year":"2016","journal-title":"Aging Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1073\/pnas.0811022106","article-title":"Soluble epoxide hydrolase plays an essential role in angiotensin II-induced cardiac hypertrophy","volume":"106","author":"Ai","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Li, L., Li, N., Pang, W., Zhang, X., Hammock, B.D., Ai, D., and Zhu, Y. (2014). Opposite effects of gene deficiency and pharmacological inhibition of soluble epoxide hydrolase on cardiac fibrosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094092"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1124\/mol.113.087122","article-title":"CYP2J2-derived epoxyeicosatrienoic acids suppress endoplasmic reticulum stress in heart failure","volume":"85","author":"Wang","year":"2014","journal-title":"Mol. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1111\/bph.12066","article-title":"Soluble epoxide hydrolase inhibitor, TUPS, protects against isoprenaline-induced cardiac hypertrophy","volume":"168","author":"Althurwi","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Westphal, C., Spallek, B., Konkel, A., Marko, L., Qadri, F., DeGraff, L.M., Schubert, C., Bradbury, J.A., Regitz-Zagrosek, V., and Falck, J.R. (2013). CYP2J2 overexpression protects against arrhythmia susceptibility in cardiac hypertrophy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073490"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/FPC.0b013e32809913ea","article-title":"CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: The Atherosclerosis Risk in Communities (ARIC) study","volume":"17","author":"Lee","year":"2007","journal-title":"Pharm. Genom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.atherosclerosis.2012.03.022","article-title":"Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease","volume":"222","author":"Theken","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1161\/01.RES.66.3.608","article-title":"Synthesis of lipoxygenase and epoxygenase products of arachidonic acid by normal and stenosed canine coronary arteries","volume":"66","author":"Rosolowsky","year":"1990","journal-title":"Circ. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.yjmcc.2018.08.027","article-title":"Endothelium-specific CYP2J2 overexpression improves cardiac dysfunction by promoting angiogenesis via Jagged1\/Notch1 signaling","volume":"123","author":"Zhao","year":"2018","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.prostaglandins.2015.01.002","article-title":"Agonists of epoxyeicosatrienoic acids reduce infarct size and ameliorate cardiac dysfunction via activation of HO-1 and Wnt1 canonical pathway","volume":"116","author":"Cao","year":"2015","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1161\/01.RES.0000139436.89654.c8","article-title":"Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42\/p44 MAPK pathway","volume":"95","author":"Seubert","year":"2004","journal-title":"Circ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.yjmcc.2006.11.020","article-title":"Mechanisms by which epoxyeicosatrienoic acids (EETs) elicit cardioprotection in rat hearts","volume":"42","author":"Gross","year":"2007","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nature01323","article-title":"Inflammation in atherosclerosis","volume":"420","author":"Libby","year":"2002","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0006-291X(90)91741-A","article-title":"14, 15-Epoxyeicosatrienoic acid promotes endothelial cell dependent adhesion of human monocytic tumor U937 cells","volume":"167","author":"Pritchard","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1161\/01.RES.88.1.44","article-title":"Endothelium-derived hyperpolarizing factor synthase (Cytochrome P450 2C9) is a functionally significant source of reactive oxygen species in coronary arteries","volume":"88","author":"Fleming","year":"2001","journal-title":"Circ. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4011","DOI":"10.1016\/j.bmcl.2003.08.060","article-title":"11,12-epoxyeicosatrienoic acid (11,12-EET): Structural determinants for inhibition of TNF-alpha-induced VCAM-1 expression","volume":"13","author":"Falck","year":"2003","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/jcp.21356","article-title":"Cytochrome P450 (CYP) 2J2 gene transfection attenuates MMP-9 via inhibition of NF-kappabeta in hyperhomocysteinemia","volume":"215","author":"Moshal","year":"2008","journal-title":"J. Cell. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"16747","DOI":"10.1073\/pnas.0508081102","article-title":"The antiinflammatory effect of laminar flow: The role of PPARgamma, epoxyeicosatrienoic acids, and soluble epoxide hydrolase","volume":"102","author":"Liu","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1161\/01.ATV.0000160340.72641.87","article-title":"Nuclear factor kappaB signaling in atherogenesis","volume":"25","author":"Kanters","year":"2005","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1161\/HYPERTENSIONAHA.119.13709","article-title":"Adenosine 2A Receptor Activation Contributes to Ang II-Induced Aortic Remodeling by Promoting Macrophage Retention","volume":"75","author":"He","year":"2020","journal-title":"Hypertension"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"719456","DOI":"10.3389\/fgene.2021.719456","article-title":"Epigenetic Regulation of Vascular Smooth Muscle Cell Phenotype Switching in Atherosclerotic Artery Remodeling: A Mini-Review","volume":"12","author":"Zurek","year":"2021","journal-title":"Front. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s11883-010-0108-5","article-title":"Soluble epoxide hydrolase in atherosclerosis","volume":"12","author":"Wang","year":"2010","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1097\/FJC.0000000000000371","article-title":"CYP2J2 Overexpression Increases EETs and Protects Against HFD-Induced Atherosclerosis in ApoE\u2212\/\u2212 Mice","volume":"67","author":"Liu","year":"2016","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/FJC.0b013e318185fa3c","article-title":"Soluble epoxide hydrolase inhibitors reduce the development of atherosclerosis in apolipoprotein e-knockout mouse model","volume":"52","author":"Ulu","year":"2008","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Tsai, M.J., Chang, W.A., Tsai, P.H., Wu, C.Y., Ho, Y.W., Yen, M.C., Lin, Y.S., Kuo, P.L., and Hsu, Y.L. (2017). Montelukast Induces Apoptosis-Inducing Factor-Mediated Cell Death of Lung Cancer Cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071353"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1161\/ATVBAHA.109.186064","article-title":"Inhibition of soluble epoxide hydrolase attenuated atherosclerosis, abdominal aortic aneurysm formation, and dyslipidemia","volume":"29","author":"Zhang","year":"2009","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.yjmcc.2016.08.001","article-title":"Inhibition of soluble epoxide hydrolase alleviated atherosclerosis by reducing monocyte infiltration in Ldlr\u2212\/\u2212 mice","volume":"98","author":"Li","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.freeradbiomed.2020.12.450","article-title":"Endothelial Nox4 dysfunction aggravates atherosclerosis by inducing endoplasmic reticulum stress and soluble epoxide hydrolase","volume":"164","author":"Yu","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.bbadis.2017.02.004","article-title":"Endothelial Nox4-based NADPH oxidase regulates atherosclerosis via soluble epoxide hydrolase","volume":"1863","author":"Hu","year":"2017","journal-title":"Biochim. Biophys. Acta. Mol. Basis Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1161\/HYPERTENSIONAHA.117.10644","article-title":"Downregulated Serum 14, 15-Epoxyeicosatrienoic Acid Is Associated with Abdominal Aortic Calcification in Patients with Primary Aldosteronism","volume":"71","author":"Liu","year":"2018","journal-title":"Hypertension"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6926","DOI":"10.1038\/s41598-017-07512-1","article-title":"Soluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced Adventitial Remodeling","volume":"7","author":"Zhou","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"50","DOI":"10.15420\/ecr.2018.33.1","article-title":"The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives","volume":"14","author":"Tsalamandris","year":"2019","journal-title":"Eur. Cardiol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Sonnweber, T., Pizzini, A., Nairz, M., Weiss, G., and Tancevski, I. (2018). Arachidonic Acid Metabolites in Cardiovascular and Metabolic Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113285"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"E715","DOI":"10.1073\/pnas.1111600109","article-title":"Diabetes promotes an inflammatory macrophage phenotype and atherosclerosis through acyl-CoA synthetase 1","volume":"109","author":"Kanter","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/ni.2022","article-title":"Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling","volume":"12","author":"Wen","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/oby.2009.227","article-title":"Expression and regulation of soluble epoxide hydrolase in adipose tissue","volume":"18","author":"Morisseau","year":"2010","journal-title":"Obesity"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1089\/scd.2010.0098","article-title":"Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPAR\u03b3","volume":"19","author":"Kim","year":"2010","journal-title":"Stem Cells Dev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1089\/scd.2016.0072","article-title":"Epoxyeicosatrienoic Acids Regulate Adipocyte Differentiation of Mouse 3T3 Cells, Via PGC-1\u03b1 Activation, Which Is Required for HO-1 Expression and Increased Mitochondrial Function","volume":"25","author":"Waldman","year":"2016","journal-title":"Stem Cells Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1194\/jlr.M053199","article-title":"Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity","volume":"55","author":"Zha","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.prostaglandins.2011.10.002","article-title":"Epoxyeicosatrienoic acids and heme oxygenase-1 interaction attenuates diabetes and metabolic syndrome complications","volume":"97","author":"Burgess","year":"2012","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"46743","DOI":"10.1038\/srep46743","article-title":"CYP2J2 and Its Metabolites EETs Attenuate Insulin Resistance via Regulating Macrophage Polarization in Adipose Tissue","volume":"7","author":"Dai","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.2337\/dc14-1720","article-title":"Type 1 diabetes mellitus and cardiovascular disease: A scientific statement from the American Heart Association and American Diabetes Association","volume":"37","author":"Fonseca","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"438","DOI":"10.2133\/dmpk.24.438","article-title":"Regulation of soluble epoxide hydrolase (sEH) in mice with diabetes: High glucose suppresses sEH expression","volume":"24","author":"Oguro","year":"2009","journal-title":"Drug Metab. Pharm."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/BJ20150397","article-title":"Down-regulation of EPHX2 gene transcription by Sp1 under high-glucose conditions","volume":"470","author":"Oguro","year":"2015","journal-title":"Biochem. J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1016\/0006-2952(89)90528-5","article-title":"Effect of diabetes and starvation on the activity of rat liver epoxide hydrolases, glutathione S-transferases and peroxisomal beta-oxidation","volume":"38","author":"Thomas","year":"1989","journal-title":"Biochem. Pharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.bbrc.2019.09.124","article-title":"Epoxyeicosatrienoic acids protect pancreatic beta cells against pro-inflammatory cytokine toxicity","volume":"520","author":"Grimes","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3840","DOI":"10.1021\/bi102070w","article-title":"20-Iodo-14,15-epoxyeicosa-8(Z)-enoyl-3-azidophenylsulfonamide: Photoaffinity labeling of a 14,15-epoxyeicosatrienoic acid receptor","volume":"50","author":"Chen","year":"2011","journal-title":"Biochemistry"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"9038","DOI":"10.1073\/pnas.1103482108","article-title":"Soluble epoxide hydrolase deficiency alters pancreatic islet size and improves glucose homeostasis in a model of insulin resistance","volume":"108","author":"Luria","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"E1097","DOI":"10.1152\/ajpendo.00216.2014","article-title":"Epoxyeicosatrienoic acids mediate insulin-mediated augmentation in skeletal muscle perfusion and blood volume","volume":"307","author":"Shim","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2013). Diagnosis and classification of diabetes mellitus. Diabetes Care, 36, S67\u2013S74.","DOI":"10.2337\/dc13-S067"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/nature05482","article-title":"Mechanisms linking obesity to insulin resistance and type 2 diabetes","volume":"444","author":"Kahn","year":"2006","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1007\/s00125-017-4260-0","article-title":"Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to insulin sensitivity in mice and in humans","volume":"60","author":"Gangadhariah","year":"2017","journal-title":"Diabetologia"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"997","DOI":"10.2337\/db09-1241","article-title":"Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db\/db mice","volume":"59","author":"Xu","year":"2010","journal-title":"Diabetes"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1210\/en.2012-2012","article-title":"CYP2J3 gene delivery up-regulated adiponectin expression via reduced endoplasmic reticulum stress in adipocytes","volume":"154","author":"Xu","year":"2013","journal-title":"Endocrinology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"E270","DOI":"10.1152\/ajpendo.00118.2014","article-title":"CYP2J2 attenuates metabolic dysfunction in diabetic mice by reducing hepatic inflammation via the PPARgamma","volume":"308","author":"Li","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1124\/jpet.109.157545","article-title":"Epoxyeicosatrienoic acid agonist rescues the metabolic syndrome phenotype of HO-2-null mice","volume":"331","author":"Sodhi","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"111149","DOI":"10.1016\/j.mce.2020.111149","article-title":"Epoxyeicosatrienoic acids improve glucose homeostasis by preventing NF-\u03baB-mediated transcription of SGLT2 in renal tubular epithelial cells","volume":"523","author":"Fu","year":"2021","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1161\/CIRCRESAHA.118.314665","article-title":"Diabetic Cardiomyopathy","volume":"124","author":"Dillmann","year":"2019","journal-title":"Circ. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1210\/en.2012-2166","article-title":"Cardiac-specific overexpression of CYP2J2 attenuates diabetic cardiomyopathy in male streptozotocin-induced diabetic mice","volume":"154","author":"Ma","year":"2013","journal-title":"Endocrinology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"H1020","DOI":"10.1152\/ajpheart.00465.2014","article-title":"Soluble epoxide hydrolase inhibition improves coronary endothelial function and prevents the development of cardiac alterations in obese insulin-resistant mice","volume":"308","author":"Roche","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3773415","DOI":"10.1155\/2022\/3773415","article-title":"Soluble Epoxide Hydrolase Inhibition Protected against Diabetic Cardiomyopathy through Inducing Autophagy and Reducing Apoptosis Relying on Nrf2 Upregulation and Transcription Activation","volume":"2022","author":"Fang","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cmet.2012.11.012","article-title":"Vascular complications of diabetes: Mechanisms of injury and protective factors","volume":"17","author":"King","year":"2013","journal-title":"Cell Metab."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.prostaglandins.2011.06.009","article-title":"Cytochrome P450 epoxygenase CYP2J2 attenuates nephropathy in streptozotocin-induced diabetic mice","volume":"96","author":"Chen","year":"2011","journal-title":"Prostaglandins Other Lipid Mediators."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/s41419-020-2594-x","article-title":"Inhibition of soluble epoxide hydrolase attenuates renal tubular mitochondrial dysfunction and ER stress by restoring autophagic flux in diabetic nephropathy","volume":"11","author":"Jiang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4468","DOI":"10.1111\/bph.15623","article-title":"Multitarget molecule, PTUPB, to treat diabetic nephropathy in rats","volume":"178","author":"Khan","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"739","DOI":"10.3389\/fphar.2019.00739","article-title":"New Lipid Mediators in Retinal Angiogenesis and Retinopathy","volume":"10","author":"Fleming","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.1167\/iovs.14-14216","article-title":"The role of cytochrome P450 epoxygenases in retinal angiogenesis","volume":"55","author":"Capozzi","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"Jama"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e129679","DOI":"10.1172\/JCI129679","article-title":"sEH promotes macrophage phagocytosis and lung clearance of Streptococcus pneumoniae","volume":"131","author":"Li","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1097\/SHK.0000000000001408","article-title":"sEH Inhibitor Tppu Ameliorates Cecal Ligation and Puncture-Induced Sepsis by Regulating Macrophage Functions","volume":"53","author":"Chen","year":"2020","journal-title":"Shock"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1097\/SHK.0000000000000767","article-title":"Soluble Epoxide Hydrolase Inhibitor Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Improves Survival in Mice","volume":"47","author":"Zhou","year":"2017","journal-title":"Shock"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"113678","DOI":"10.1016\/j.ejmech.2021.113678","article-title":"Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis","volume":"223","author":"Du","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"109907","DOI":"10.1016\/j.biopha.2020.109907","article-title":"A COX-2\/sEH dual inhibitor PTUPB ameliorates cecal ligation and puncture-induced sepsis in mice via anti-inflammation and anti-oxidative stress","volume":"126","author":"Zhang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s12931-021-01891-w","article-title":"CYP2J2 and EETs protect against pulmonary arterial hypertension with lung ischemia-reperfusion injury in vivo and in vitro","volume":"22","author":"Ding","year":"2021","journal-title":"Respir. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1159\/000362950","article-title":"CYP2J2 and EETs Protect against Oxidative Stress and Apoptosis in vivo and in vitro Following Lung Ischemia\/Reperfusion","volume":"33","author":"Chen","year":"2014","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s10753-018-0758-y","article-title":"Effect of Soluble Epoxide Hydrolase in Hyperoxic Acute Lung Injury in Mice","volume":"41","author":"Li","year":"2018","journal-title":"Inflammation"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Liu, L.P., Li, B., Shuai, T.K., Zhu, L., and Li, Y.M. (2018). Deletion of soluble epoxide hydrolase attenuates mice Hyperoxic acute lung injury. BMC Anesthesiol., 18.","DOI":"10.1186\/s12871-018-0490-z"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1097\/SHK.0000000000001067","article-title":"Soluble Epoxide Hydrolase Plays a Vital Role in Angiotensin II-Induced Lung Injury in Mice","volume":"50","author":"Tao","year":"2018","journal-title":"Shock"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10753-016-0448-6","article-title":"Soluble Epoxide Hydrolase Inhibitor Suppresses the Expression of Triggering Receptor Expressed on Myeloid Cells-1 by Inhibiting NF-kB Activation in Murine Macrophage","volume":"40","author":"Dong","year":"2017","journal-title":"Inflammation"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.tox.2017.07.002","article-title":"Soluble epoxide hydrolase inhibitor AUDA decreases bleomycin-induced pulmonary toxicity in mice by inhibiting the p38\/Smad3 pathways","volume":"389","author":"Dong","year":"2017","journal-title":"Toxicology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00441-015-2262-0","article-title":"Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice","volume":"363","author":"Zhou","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1073\/pnas.0409591102","article-title":"Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor","volume":"102","author":"Smith","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1165\/rcmb.2011-0359OC","article-title":"Use of a soluble epoxide hydrolase inhibitor in smoke-induced chronic obstructive pulmonary disease","volume":"46","author":"Wang","year":"2012","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s10753-016-0495-z","article-title":"Cigarette Smoke-Induced Pulmonary Inflammation and Autophagy Are Attenuated in Ephx2-Deficient Mice","volume":"40","author":"Li","year":"2017","journal-title":"Inflammation"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.plefa.2014.10.006","article-title":"Epoxyeicosatrienoic acids attenuate cigarette smoke extract-induced interleukin-8 production in bronchial epithelial cells","volume":"94","author":"Ma","year":"2015","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"L970","DOI":"10.1152\/ajplung.00161.2016","article-title":"14,15-Epoxyeicosatrienoic acid suppresses cigarette smoke condensate-induced inflammation in lung epithelial cells by inhibiting autophagy","volume":"311","author":"Li","year":"2016","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/nm748","article-title":"Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4)","volume":"8","author":"Levy","year":"2002","journal-title":"Nat. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.1365-2133.2012.11177.x","article-title":"Efficacy and safety of 15(R\/S)-methyl-lipoxin A(4) in topical treatment of infantile eczema","volume":"168","author":"Wu","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1165\/rcmb.2013-0440OC","article-title":"Soluble epoxide hydrolase inhibitor attenuates inflammation and airway hyperresponsiveness in mice","volume":"52","author":"Yang","year":"2015","journal-title":"Am. J. Respir Cell Mol. Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"172874","DOI":"10.1016\/j.ejphar.2019.172874","article-title":"Inhibition of soluble epoxide hydrolase attenuates airway remodeling in a chronic asthma model","volume":"868","author":"Jiang","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.3389\/fphar.2019.01118","article-title":"Effect of Dual sEH\/COX-2 Inhibition on Allergen-Induced Airway Inflammation","volume":"10","author":"Dileepan","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/cjp.cjp_80_21","article-title":"Epoxyeicosatrienoic acids and soluble epoxide hydrolase in physiology and diseases of the central nervous system","volume":"65","author":"Kuo","year":"2022","journal-title":"Chin. J. Physiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.prostaglandins.2012.09.004","article-title":"Cytochrome P450 2J2 is protective against global cerebral ischemia in transgenic mice","volume":"99","author":"Li","year":"2012","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1038\/sj.jcbfm.9600494","article-title":"Soluble epoxide hydrolase: A novel therapeutic target in stroke","volume":"27","author":"Zhang","year":"2007","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/s12031-015-0670-y","article-title":"Epoxyeicosanoid Signaling Provides Multi-target Protective Effects on Neurovascular Unit in Rats After Focal Ischemia","volume":"58","author":"Liu","year":"2016","journal-title":"J. Mol. Neurosci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1007\/s12035-015-9118-1","article-title":"Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury","volume":"53","author":"Chen","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s12974-021-02255-3","article-title":"EETs\/sEHi alleviates nociception by blocking the crosslink between endoplasmic reticulum stress and neuroinflammation in a central poststroke pain model","volume":"18","author":"Liu","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Neuschwander-Tetri, B.A. (2017). Non-alcoholic fatty liver disease. BMC Med., 15.","DOI":"10.1186\/s12916-017-0806-8"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1124\/mol.117.111047","article-title":"Effects of Farnesoid X Receptor Activation on Arachidonic Acid Metabolism, NF-kB Signaling, and Hepatic Inflammation","volume":"94","author":"Gai","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Liu, Y., Dang, H., Li, D., Pang, W., Hammock, B.D., and Zhu, Y. (2012). Inhibition of soluble epoxide hydrolase attenuates high-fat-diet-induced hepatic steatosis by reduced systemic inflammatory status in mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039165"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"14189","DOI":"10.1074\/jbc.M113.458414","article-title":"Soluble epoxide hydrolase deficiency or inhibition attenuates diet-induced endoplasmic reticulum stress in liver and adipose tissue","volume":"288","author":"Bettaieb","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.yexcr.2019.04.029","article-title":"Epoxyeicosatrienoic intervention improves NAFLD in leptin receptor deficient mice by an increase in PGC1\u03b1-HO-1-PGC1\u03b1-mitochondrial signaling","volume":"380","author":"Raffaele","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.bbrc.2019.12.131","article-title":"PTUPB ameliorates high-fat diet-induced non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in mice","volume":"523","author":"Sun","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.taap.2015.03.022","article-title":"Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice","volume":"286","author":"Harris","year":"2015","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.clinre.2017.09.001","article-title":"Soluble epoxide hydrolase inhibition with t-TUCB alleviates liver fibrosis and portal pressure in carbon tetrachloride-induced cirrhosis in rats","volume":"42","author":"Zhang","year":"2018","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"761517","DOI":"10.3389\/fmed.2021.761517","article-title":"COX-2\/sEH Dual Inhibitor PTUPB Alleviates CCl (4) -Induced Liver Fibrosis and Portal Hypertension","volume":"8","author":"Zhao","year":"2021","journal-title":"Front. Med."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.prostaglandins.2017.08.004","article-title":"Inhibition of soluble epoxide hydrolase lowers portal hypertension in cirrhotic rats by ameliorating endothelial dysfunction and liver fibrosis","volume":"131","author":"Deng","year":"2017","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"117327","DOI":"10.1016\/j.lfs.2020.117327","article-title":"CYP2J2-produced epoxyeicosatrienoic acids attenuate ischemia\/reperfusion-induced acute kidney injury by activating the SIRT1-FoxO3a pathway","volume":"246","author":"Zhu","year":"2020","journal-title":"Life Sci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1046\/j.1523-1755.2003.00036.x","article-title":"Contributions of nitric oxide, EDHF, and EETs to endothelium-dependent relaxation in renal afferent arterioles","volume":"63","author":"Wang","year":"2003","journal-title":"Kidney Int."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"12608","DOI":"10.1073\/pnas.1705615114","article-title":"Epoxide metabolites of arachidonate and docosahexaenoate function conversely in acute kidney injury involved in GSK3\u03b2 signaling","volume":"114","author":"Deng","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"F971","DOI":"10.1152\/ajprenal.00256.2014","article-title":"Inhibition of soluble epoxide hydrolase prevents renal interstitial fibrosis and inflammation","volume":"307","author":"Kim","year":"2014","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1111\/febs.14100","article-title":"Podocyte-specific soluble epoxide hydrolase deficiency in mice attenuates acute kidney injury","volume":"284","author":"Bettaieb","year":"2017","journal-title":"FEBS J."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s10565-008-9071-0","article-title":"Attenuation of cisplatin nephrotoxicity by inhibition of soluble epoxide hydrolase","volume":"25","author":"Parrish","year":"2009","journal-title":"Cell Biol. Toxicol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"F576","DOI":"10.1152\/ajprenal.00288.2016","article-title":"The epoxyeicosatrienoic acid analog PVPA ameliorates cyclosporine-induced hypertension and renal injury in rats","volume":"311","author":"Yeboah","year":"2016","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"9074","DOI":"10.1096\/fj.202000415R","article-title":"Soluble epoxide hydrolase inhibitor, TPPU, increases regulatory T cells pathway in an arthritis model","volume":"34","author":"Abdalla","year":"2020","journal-title":"FASEB J."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"106841","DOI":"10.1016\/j.intimp.2020.106841","article-title":"Peripheral soluble epoxide hydrolase inhibition reduces hypernociception and inflammation in albumin-induced arthritis in temporomandibular joint of rats","volume":"87","author":"Teixeira","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"76","DOI":"10.17085\/apm.2019.14.1.76","article-title":"Analgesic effects of soluble epoxide hydrolase inhibitor in K\/BxN serum transfer arthritis mouse model","volume":"14","author":"Park","year":"2019","journal-title":"Anesth. Pain Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3389\/fphar.2019.00533","article-title":"Pharmaceutical Effects of Inhibiting the Soluble Epoxide Hydrolase in Canine Osteoarthritis","volume":"10","author":"McReynolds","year":"2019","journal-title":"Front. Pharm."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/art.42000","article-title":"Clinical and Preclinical Evidence for Roles of Soluble Epoxide Hydrolase in Osteoarthritis Knee Pain","volume":"74","author":"Gowler","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"685824","DOI":"10.3389\/fvets.2021.685824","article-title":"Targeting Soluble Epoxide Hydrolase and Cyclooxygenases Enhance Joint Pain Control, Stimulate Collagen Synthesis, and Protect Chondrocytes from Cytokine-Induced Apoptosis","volume":"8","author":"Tucker","year":"2021","journal-title":"Front. Vet. Sci."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/12\/3873\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:33:05Z","timestamp":1760139185000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/12\/3873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,16]]},"references-count":165,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["molecules27123873"],"URL":"https:\/\/doi.org\/10.3390\/molecules27123873","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,16]]}}}