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Sacubitril Ameliorates Cardiac Fibrosis Through Inhibiting TRPM7 Channel.

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.

SUBMITTER: Jia T

PROVIDER: S-EPMC8586221 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Sacubitril Ameliorates Cardiac Fibrosis Through Inhibiting TRPM7 Channel.

Jia Tian T Wang Xiaozhi X Tang Yiqun Y Yu Wenying W Li Chenhui C Cui Shufang S Zhu Juanjuan J Meng Wei W Wang Chen C Wang Quanyi Q

Frontiers in cell and developmental biology 20211029

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 Ca<sup>2+</sup> influx. Transient receptor potential cation channel subfamily M member 7 (TRPM7), the major Ca<sup>2+</sup> permeable channel, plays a regulatory role in cardiac fibrosis. In this study, we sought to explore the mechanistic details for ...[more]

PMID: 34778271

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Sacubitril Ameliorates Cardiac Fibrosis Through Inhibiting TRPM7 Channel.

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Sacubitril Ameliorates Cardiac Fibrosis Through Inhibiting TRPM7 Channel.

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