Back to Search
Start Over
Sacubitril Ameliorates Cardiac Fibrosis Through Inhibiting TRPM7 Channel
- Source :
- Frontiers in Cell and Developmental Biology, Vol 9 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- Heart failure caused by cardiac fibrosis has become a major challenge of public health worldwide. Cardiomyocyte programmed cell death (PCD) and activation of fibroblasts are crucial pathological features, both of which are associated with aberrant Ca2+ influx. Transient receptor potential cation channel subfamily M member 7 (TRPM7), the major Ca2+ permeable channel, plays a regulatory role in cardiac fibrosis. In this study, we sought to explore the mechanistic details for sacubitril, a component of sacubitril/valsartan, in treating cardiac fibrosis. We demonstrated that sacubitril/valsartan could effectively ameliorate cardiac dysfunction and reduce cardiac fibrosis induced by isoprotereno (ISO) in vivo. We further investigated the anti-fibrotic effect of sacubitril in fibroblasts. LBQ657, the metabolite of sacubitril, could significantly attenuate transforming growth factor-β 1 (TGF-β1) induced cardiac fibrosis by blocking TRPM7 channel, rather than suppressing its protein expression. In addition, LBQ657 reduced hypoxia-induced cardiomyocyte PCD via suppression of Ca2+ influx regulated by TRPM7. These findings suggested that sacubitril ameliorated cardiac fibrosis by acting on both fibroblasts and cardiomyocytes through inhibiting TRPM7 channel.
- Subjects :
- sacubitril
cardiac fibrosis
PCD
TRPM7
Ca2+ influx
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 2296634X
- Volume :
- 9
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Cell and Developmental Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.b65a1a8a3abd44d1a4fe848d33d4e926
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fcell.2021.760035