title: Increasing TRPV4 expression restores flow-induced dilation impaired in mesenteric arteries with aging.
abstract: The flow-stimulated intracellular Ca(2+) concentration ([Ca(2+)]i) rise in endothelial cells is an important early event leading to flow-induced blood vessel dilation. Transient receptor potential vanilloid subtype 4 (TRPV4), a Ca(2+)-permeable cation channel, facilitates the flow-stimulated [Ca(2+)]i 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(2+) imaging, immunoblotting, and immunostaining assays in rats. We found that the flow-induced and TRPV4 activator 4α-PDD-induced dilation of mesenteric arteries from aged rats were significantly decreased compared with those from young rats. The flow- or 4α-PDD-induced [Ca(2+)]i 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 4α-PDD-induced NO production was significantly reduced in aged MAECs. Compared with lentiviral GFP-treated aged rats, lentiviral vector delivery of TRPV4 increased TRPV4 expression level in aged MAECs and restored the flow- and 4α-PDD-induced vessel dilation in aged mesenteric arteries. We concluded that impaired TRPV4-mediated Ca(2+) signaling causes endothelial dysfunction and that TRPV4 is a potential target for clinical treatment of age-related vascular system diseases.
authors.affiliation: Department of Physiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Physiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Jizheng
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Peking 100191, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Physiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Dejun
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Physiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Physiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Zhongwen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Jinhang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Physiology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.|Central laboratory of molecular and cellular biology of School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009213:Myography; D009569:Nitric Oxide / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D051381:Rats; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism*
chemical_list: D010703:Phorbol Esters; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; C008876:phorbol-12,13-didecanoate; D009569:Nitric Oxide; D002118:Calcium