TRPM4 Modulates Right Ventricular Remodeling Under Pressure Load Accompanied With Decreased Expression Level.
TRPM4
cardiac hypertrophy
monocrotaline
pulmonary hypertension
rat
right ventricular failure
Journal
Journal of cardiac failure
ISSN: 1532-8414
Titre abrégé: J Card Fail
Pays: United States
ID NLM: 9442138
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
28
04
2019
revised:
06
02
2020
accepted:
19
02
2020
pubmed:
10
3
2020
medline:
19
8
2021
entrez:
10
3
2020
Statut:
ppublish
Résumé
Survival of patients with congenital heart defects including increased right ventricular pressure load (ie, tetralogy of Fallot) or pulmonary hypertension is dependent on the function of the right ventricle (RV). RV remodeling has several effects with progressive transition from compensated status to heart failure. Transient receptor potential melastatin 4 (TRPM4) forms cation channels expressed in myocardium, which was shown to modulate cardiac remodeling in the left ventricle of mice. Aim of this study was to identify the role of TRPM4 for contractile function and remodeling of the RV in a rat model of right ventricular pressure load. We performed experiments with untreated rats and under monocrotaline (MCT)-induced pressure load comparing wild-type (Trpm4 Right ventricular pressure load evoked by MCT treatment in rats leads to a prominent downregulation of TRPM4 protein expression in the RV and complete deletion of TRPM4 expression aggravates right ventricular hypertrophy. Thus, therapeutic modulation of TRPM4 expression and activity might represent a novel approach to target right ventricular remodeling in patients with pulmonary hypertension or otherwise loaded RV.
Sections du résumé
BACKGROUND
BACKGROUND
Survival of patients with congenital heart defects including increased right ventricular pressure load (ie, tetralogy of Fallot) or pulmonary hypertension is dependent on the function of the right ventricle (RV). RV remodeling has several effects with progressive transition from compensated status to heart failure. Transient receptor potential melastatin 4 (TRPM4) forms cation channels expressed in myocardium, which was shown to modulate cardiac remodeling in the left ventricle of mice. Aim of this study was to identify the role of TRPM4 for contractile function and remodeling of the RV in a rat model of right ventricular pressure load.
METHODS AND RESULTS
RESULTS
We performed experiments with untreated rats and under monocrotaline (MCT)-induced pressure load comparing wild-type (Trpm4
CONCLUSIONS
CONCLUSIONS
Right ventricular pressure load evoked by MCT treatment in rats leads to a prominent downregulation of TRPM4 protein expression in the RV and complete deletion of TRPM4 expression aggravates right ventricular hypertrophy. Thus, therapeutic modulation of TRPM4 expression and activity might represent a novel approach to target right ventricular remodeling in patients with pulmonary hypertension or otherwise loaded RV.
Identifiants
pubmed: 32147520
pii: S1071-9164(19)30440-3
doi: 10.1016/j.cardfail.2020.02.006
pii:
doi:
Substances chimiques
TRPM Cation Channels
0
TRPM4 protein, human
0
TRPM4 protein, mouse
0
TRPM4 protein, rat
0
Monocrotaline
73077K8HYV
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
599-609Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.