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Transient receptor potential vanilloid subtype 4 (TRPV4), a Ca<jats:sup>2+<\/jats:sup>-permeable cation channel, facilitates the flow-stimulated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> rise. To determine whether TRPV4 is involved in age-related flow-induced blood vessel dilation impairment, we measured blood vessel diameter and nitric oxide (NO) levels and performed Ca<jats:sup>2+<\/jats:sup> imaging, immunoblotting and immunostaining assays in rats. We found that the flow-induced and TRPV4 activator 4\u03b1-PDD-induced dilation of mesenteric arteries from aged rats were significantly decreased compared with those from young rats. The flow- or 4\u03b1-PDD-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> rise was also markedly reduced in primary cultured mesenteric artery endothelial cells (MAECs) from aged rats. Immunoblotting and immunostaining results showed an age-related decrease of TRPV4 expression levels in MAECs. Additionally, the 4\u03b1-PDD-induced NO production was significantly reduced in aged MAECs. Compared with lentiviral GFP-treated aged rats, lentiviral vector delivery of <jats:italic>TRPV4<\/jats:italic> increased TRPV4 expression level in aged MAECs and restored the flow- and 4\u03b1-PDD-induced vessel dilation in aged mesenteric arteries. We concluded that impaired TRPV4-mediated Ca<jats:sup>2+<\/jats:sup> signaling causes endothelial dysfunction and that TRPV4 is a potential target for clinical treatment of age-related vascular system diseases.<\/jats:p>","DOI":"10.1038\/srep22780","type":"journal-article","created":{"date-parts":[[2016,3,7]],"date-time":"2016-03-07T10:34:39Z","timestamp":1457346879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Increasing TRPV4 expression restores flow-induced dilation impaired in mesenteric arteries with aging"],"prefix":"10.1038","volume":"6","author":[{"given":"Juan","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizheng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongwen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,7]]},"reference":[{"key":"BFsrep22780_CR1","doi-asserted-by":"crossref","unstructured":"Bevan, J. 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