Research Papers:

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 and Zheng Gen Jin _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:37622-37635. https://doi.org/10.18632/oncotarget.9376

Metrics: PDF 2166 views  |   HTML 2662 views  |   ?  


Suowen Xu1, Bin Liu1, Meimei Yin1, Marina Koroleva1, Michael Mastrangelo1, Sara Ture1, Craig N. Morrell1, David X. Zhang2, Edward A. Fisher3 and Zheng Gen Jin1

1 Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

2 Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

3 Department of Medicine, Division of Cardiology, and The Marc and Ruti Bell Program in Vascular Biology, New York University School of Medicine, New York, NY, USA

Correspondence to:

Zheng Gen Jin, email:

Keywords: AMPK, atherosclerosis, GSK1016790A, shear stress, TRPV4

Received: December 29, 2015 Accepted: April 29, 2016 Published: May 14, 2016


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 9376