Referenced in: none

Automatically associated channels: SK1 , TRP , TRPV , TRPV4

Title: A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis.

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

Journal, date & volume: Oncotarget, 2016 May 14 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/27191895

Abstract
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.