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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 4?-PDD-induced dilation of mesenteric arteries from aged rats were significantly decreased compared with those from young rats. The flow- or 4?-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 4?-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 4?-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.

SUBMITTER: Du J 

PROVIDER: S-EPMC4780030 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Increasing TRPV4 expression restores flow-induced dilation impaired in mesenteric arteries with aging.

Du Juan J   Wang Xia X   Li Jie J   Guo Jizheng J   Liu Limei L   Yan Dejun D   Yang Yunyun Y   Li Zhongwen Z   Zhu Jinhang J   Shen Bing B  

Scientific reports 20160307


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+) imagin  ...[more]

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