{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:39:38Z","timestamp":1780922378328,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T00:00:00Z","timestamp":1534118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600314"],"award-info":[{"award-number":["81600314"]}],"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":["81630030"],"award-info":[{"award-number":["81630030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic drinking leads to myocardial contractile dysfunction and dilated cardiomyopathy, and cardiac fibrosis is a consequence of these alcoholic injuries. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) to less bioactive diols, and EETs have cardioprotective properties. However, the effects of sEH inhibition in ethanol (EtOH)\u2010induced cardiac fibrosis are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study was designed to investigate the role and underlying mechanisms of sEH inhibition in chronic EtOH feeding\u2010induced cardiac fibrosis. C57BL\/6J mice were fed a 4% Lieber\u2010DeCarli EtOH diet for 8\u00a0weeks, and the sEH inhibitor 1\u2010trifluoromethoxyphenyl\u20103\u2010(1\u2010propionylpiperidin\u20104\u2010yl) urea (TPPU) was administered throughout the experimental period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that chronic EtOH intake led to cardiac dilatation, collagen deposition, and autophagosome accumulation, while TPPU administration ameliorated these effects. In vitro, treating primary cardiac fibroblasts (CFs) with EtOH resulted in CF activation, including alpha smooth muscle actin overexpression, collagen synthesis, and cell migration. Moreover, EtOH disturbed CF autophagic flux, as evidenced by the increased LC3 II\/I ratio and SQSTM1 expression, and by the enhanced autophagosome accumulation. TPPU treatment prevented the activation of CF induced by EtOH and restored the impaired autophagic flux by suppressing mTOR activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these findings suggest that sEH pharmacological inhibition may be a unique therapeutic strategy for treating EtOH\u2010induced cardiac fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13847","type":"journal-article","created":{"date-parts":[[2018,7,26]],"date-time":"2018-07-26T14:14:31Z","timestamp":1532614471000},"page":"1970-1978","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Pharmacological Inhibition of Soluble Epoxide Hydrolase Ameliorates Chronic Ethanol\u2010Induced Cardiac Fibrosis by Restoring Autophagic Flux"],"prefix":"10.1111","volume":"42","author":[{"given":"Chi","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Internal 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