ArticleThe Journal of clinical investigation2003
Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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Who cites it
160 citing papers in PubMed, 275 citations in OpenAlex.
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- An optimized plasmalogen modulating dietary supplement provides greater protection in a male than female mouse model of dilated cardiomyopathy.Journal of molecular and cellular cardiology plus · 2025Article
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- Heart failure, inflammation and exercise.International journal of biological sciences · 2025Review
- α-Bisabolol: A Dietary Sesquiterpene that Attenuates Apoptotic and Nonapoptotic Cell Death Pathways by Regulating the Mitochondrial Biogenesis and Endoplasmic Reticulum Stress-Hippo Signaling Axis in Doxorubicin-Induced Acute Cardiotoxicity in Rats.ACS pharmacology & translational science · 2024Article
- Inhibiting endothelial cell Mst1 attenuates acute lung injury in mice.JCI insight · 2024Article
- Distinct functional and molecular profiles between physiological and pathological atrial enlargement offer potential new therapeutic opportunities for atrial fibrillation.Clinical science (London, England : 1979) · 2024Article
- Mst1-mediated phosphorylation of FoxO1 and C/EBP-β stimulates cell-protective mechanisms in cardiomyocytes.Nature communications · 2024Article
- Circular RNAs: a small piece in the heart failure puzzle.Functional & integrative genomics · 2024Review
- Regenerative loss in the animal kingdom as viewed from the mouse digit tip and heart.Developmental biology · 2024Review
- MicroRNA205: A Key Regulator of Cardiomyocyte Transition from Proliferative to Hypertrophic Growth in the Neonatal Heart.International journal of molecular sciences · 2024Article
- Shikonin alleviates doxorubicin-induced cardiotoxicity via Mst1/Nrf2 pathway in mice.Scientific reports · 2024Article
- MST1 mediates doxorubicin-induced cardiomyopathy by SIRT3 downregulation.Cellular and molecular life sciences : CMLS · 2023Article
- IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death.JACC. Basic to translational science · 2023Article
- Mouse models of spontaneous atrial fibrillation.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- ZBP1 Protects Against mtDNA-Induced Myocardial Inflammation in Failing Hearts.Circulation research · 2023Article
100 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of mammalian sterile 20-like kinase 1 (Mst1) by genotoxic compounds is known to stimulate apoptosis in some cell types. The importance of Mst1 in cell death caused by clinically relevant pathologic stimuli is unknown, however. In this study, we show that Mst1 is a prominent myelin basic protein kinase activated by proapoptotic stimuli in cardiac myocytes and that Mst1 causes cardiac myocyte apoptosis in vitro in a kinase activity-dependent manner. In vivo, cardiac-specific overexpression of Mst1 in transgenic mice results in activation of caspases, increased apoptosis, and dilated cardiomyopathy. Surprisingly, however, Mst1 prevents compensatory cardiac myocyte elongation or hypertrophy despite increased wall stress, thereby obscuring the use of the Frank-Starling mechanism, a fundamental mechanism by which the heart maintains cardiac output in response to increased mechanical load at the single myocyte level. Furthermore, Mst1 is activated by ischemia/reperfusion in the mouse heart in vivo. Suppression of endogenous Mst1 by cardiac-specific overexpression of dominant-negative Mst1 in transgenic mice prevents myocyte death by pathologic insults. These results show that Mst1 works as both an essential initiator of apoptosis and an inhibitor of hypertrophy in cardiac myocytes, resulting in a previously unrecognized form of cardiomyopathy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.