A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis. Oncotarget 2016 Jun 21;7(25):37622-37635
Date
10/23/2016Pubmed ID
27191895Pubmed Central ID
PMC5122337DOI
10.18632/oncotarget.9376Scopus ID
2-s2.0-84978176831 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
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.
Author List
Xu S, Liu B, Yin M, Koroleva M, Mastrangelo M, Ture S, Morrell CN, Zhang DX, Fisher EA, Jin ZGAuthor
David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAtherosclerosis
Cell Adhesion
Gene Knockdown Techniques
Human Umbilical Vein Endothelial Cells
Humans
Leucine
Male
Mice
Mice, Inbred C57BL
Monocytes
Sulfonamides
TRPV Cation Channels
U937 Cells
