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Omega-3 also have anti-inflammatory and plaque-stabilization effects and regulate vasodilation and constriction. However, there are few studies of the role of omega-3 in flow-induced vasodilation involving Ca2+-permeable ion channel TRPV4 in high-fat diet-induced obese (DIO) mouse. Here, we determined whether omega-3 protect against vascular dysfunction induced by a high-fat diet by enhancing TRPV4 activity and subsequently improving flow-mediated vasodilation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Flow-mediated vasodilation in second-order mesenteric arteries from mice was measured using a pressure myograph. The intracellular Ca2+ concentration in response to flow and GSK1016790A (a TRPV4 agonist) was measured by Fluo-4 fluorescence. Whole-cell current was measured by patch clamp. Cell membrane tether force was measured by atomic force microscopy. Impairment of flow-mediated vasodilation in arteries and Ca2+ influx in endothelial cells from DIO mice was restored by omega-3 treatment. The improved flow-induced vasodilation was inhibited by the TRPV4 antagonist HC067047 and in TRPV4\u2212\/\u2212 mice. Omega-3 treatment enhanced endothelial TRPV4 activity and altered cell membrane mechanic property, as indicated by enhanced GSK1016790A-induced Ca2+ influx and whole-cell current and altered membrane mean tether force in endothelial cells from DIO mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Omega-3 improve vascular function by improving flow-induced vasodilation via enhancing TRPV4 activity in the endothelium of obese mice which may be related to improved cell membrane physical property. Activation of TRPV4 in endothelium plays an important role in the protective mechanisms of omega-3 against vascular dysfunction in obesity by improving flow-mediated vasodilation.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cvr\/cvaa296","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T11:13:56Z","timestamp":1602069236000},"page":"2450-2458","source":"Crossref","is-referenced-by-count":29,"title":["Omega-3 fatty acids improve flow-induced vasodilation by enhancing TRPV4 in arteries from diet-induced obese mice"],"prefix":"10.1093","volume":"117","author":[{"given":"Yifei","family":"Zhu","sequence":"first","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University 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