Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/208403
Title: | TRPV4 Channels Promote Pathological, but Not Physiological, Cardiac Remodeling through the Activation of Calcineurin/NFAT and TRPC6 |
Author: | Yáñez Bisbe, Laia Moya, Mar Rodríguez Sinovas, Antonio Ruiz Meana, Marisol Inserte, Javier Tajes, Marta Batlle, Montserrat Guasch, Eduard Mas Stachurska, Aleksandra Miró, Elisabet Rivas, Nuria Ferreira González, Ignacio Garcia Elias, Anna Benito, Begoña |
Keywords: | Insuficiència cardíaca Ratolins transgènics Heart Failure Mice, Transgenic |
Issue Date: | 26-Jan-2024 |
Publisher: | MDPI AG |
Abstract: | TRPV4 channels, which respond to mechanical activation by permeating Ca2+ into the cell, may play a pivotal role in cardiac remodeling during cardiac overload. Our study aimed to investigate TRPV4 involvement in pathological and physiological remodeling through Ca2+-dependent signaling. TRPV4 expression was assessed in heart failure (HF) models, induced by isoproterenol infusion or transverse aortic constriction, and in exercise-induced adaptive remodeling models. The impact of genetic TRPV4 inhibition on HF was studied by echocardiography, histology, gene and protein analysis, arrhythmia inducibility, Ca2+ dynamics, calcineurin (CN) activity, and NFAT nuclear translocation. TRPV4 expression exclusively increased in HF models, strongly correlating with fibrosis. Isoproterenol-administered transgenic TRPV4-/- mice did not exhibit HF features. Cardiac fibroblasts (CFb) from TRPV4+/+ animals, compared to TRPV4-/-, displayed significant TRPV4 overexpression, elevated Ca2+ influx, and enhanced CN/NFATc3 pathway activation. TRPC6 expression paralleled that of TRPV4 in all models, with no increase in TRPV4-/- mice. In cultured CFb, the activation of TRPV4 by GSK1016790A increased TRPC6 expression, which led to enhanced CN/NFATc3 activation through synergistic action of both channels. In conclusion, TRPV4 channels contribute to pathological remodeling by promoting fibrosis and inducing TRPC6 upregulation through the activation of Ca2+-dependent CN/NFATc3 signaling. These results pose TRPV4 as a primary mediator of the pathological response. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/ijms25031541 |
It is part of: | International Journal of Molecular Sciences, 2024, vol. 25, num. 3, p. 1541 |
URI: | http://hdl.handle.net/2445/208403 |
Related resource: | https://doi.org/10.3390/ijms25031541 |
ISSN: | 1422-0067 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
ijms-25-01541.pdf | 3.85 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License