A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis

Suowen Xu, Bin Liu, Meimei Yin, Marina Koroleva, Michael Mastrangelo, Sara Ture, Craig N. Morrell, David X. Zhang, Edward A. Fisher, Zheng Gen Jin

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


TRPV4 ion channel mediates vascular mechanosensitivity and vasodilation. Here, we sought to explore whether non-mechanical activation of TRPV4 could limit vascular inflammation and atherosclerosis. We found that GSK1016790A, a potent and specific small-molecule agonist of TRPV4, induces the phosphorylation and activation of eNOS partially through the AMPK pathway. Moreover, GSK1016790A inhibited TNF-α-induced monocyte adhesion to human endothelial cells. Mice given GSK1016790A showed increased phosphorylation of eNOS and AMPK in the aorta and decreased leukocyte adhesion to TNF-α-inflamed endothelium. Importantly, oral administration of GSK1016790A reduced atherosclerotic plaque formation in ApoE deficient mice fed a Western-type diet. Together, the present study suggests that pharmacological activation of TRPV4 may serve as a potential therapeutic approach to treat atherosclerosis.

Original languageEnglish
Pages (from-to)37622-37635
Number of pages14
Issue number25
StatePublished - 2016
Externally publishedYes


  • AMPK
  • Atherosclerosis
  • GSK1016790A
  • Shear stress
  • TRPV4


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