TMAO Impairs Mouse Aortic Vasodilation by Inhibiting TRPV4 Channels in Endothelial Cells

Trimethylamine oxide (TMAO) is an intestinal flora metabolite associated with risk of cardiovascular diseases. Transient receptor potential vanilloid 4 (TRPV4) is a Ca 2+ -permeable ion channel that is essential for vasodilation and endothelial function. Currently, there are few studies on the effec...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cardiovascular translational research 2024-12, Vol.17 (6), p.1415-1426
Main Authors: Zhang, Ning, Liu, Liangju, Lv, Xiaowang, Wang, Yixuan, Zhang, Wei, Wen, Xin, Yu, Fan, Zhou, Tingting
Format: Article
Language:English
Subjects:
Animals
Aorta - drug effects
Aorta - metabolism
Aorta - physiopathology
Biomedical Engineering and Bioengineering
Biomedicine
Calcium Signaling - drug effects
Cardiology
Cells, Cultured
Dose-Response Relationship, Drug
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Endothelial Cells - pathology
Human Genetics
Humans
Male
Medicine
Medicine & Public Health
Membrane Potentials
Methylamines - metabolism
Methylamines - pharmacology
Mice
Mice, Inbred C57BL
Original Article
Signal Transduction
TRPV Cation Channels - metabolism
Vasodilation - drug effects
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Trimethylamine oxide (TMAO) is an intestinal flora metabolite associated with risk of cardiovascular diseases. Transient receptor potential vanilloid 4 (TRPV4) is a Ca 2+ -permeable ion channel that is essential for vasodilation and endothelial function. Currently, there are few studies on the effect of TMAO on TRPV4 channels. In the present study, Ca 2+ imaging of vascular tissue showed that TMAO inhibited TRPV4-mediated Ca 2+ influx into aortic endothelial cells in a dose-dependent manner. Furthermore, a whole-cell patch clamp assay showed that TMAO blocked TRPV4-mediated cation currents. Notably, results of aortic vascular tension measurement showed that TMAO impaired endothelium-dependent vasodilation in mouse aortic vessels through the TRPV4-NO pathway. Our results indicated that TMAO inhibited Ca 2+ entry in endothelial cells and impaired vasodilation through the TRPV4-NO pathway in mice. These results provide scientific evidence for novel pathogenic mechanisms underlying the role of TMAO in cardiovascular disease. Graphical Abstract TMAO impairs mouse aortic vasodilation by inhibiting TRPV4-NO pathway in endothelial cells.
ISSN:1937-5387
1937-5395
1937-5395
DOI:10.1007/s12265-024-10543-5