ArticleBasic research in cardiology2019
Increased calpain-1 in mitochondria induces dilated heart failure in mice: role of mitochondrial superoxide anion.
Article in Basic research in cardiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 80 citations in OpenAlex.
- Simvastatin Combined with Resistance Training Improves Outcomes in Patients with Chronic Heart Failure by Modulating Mitochondrial Membrane Potential and the Janus Kinase/Signal Transducer and Activator of Transcription 3 Signaling Pathways.Cardiovascular therapeutics · 2022Trial
- Inhibition of calpain-mediated HMGB1 alleviates cardiac inflammation and dysfunction induced by ultra-processed foods.JCI insight · 2026Article
- Mitofilin Preservation Mitigates Cardiac Injury in Donation-After-Circulatory-Death Hearts.Cells · 2026Article
- Severe Dilated Cardiomyopathy with PLACK Syndrome Caused by a Novel Truncating Variant in the CAST Gene.Genes · 2025Article
- Precision Medicine: Therapeutically Targeting Mitochondrial Alterations in Heart Failure.JACC. Basic to translational science · 2025Review
- Mitochondrial Transport Proteins in Cardiovascular Diseases: Metabolic Gatekeepers, Pathogenic Mediators and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Cannabidiol Prevents Heart Failure Dysfunction and Remodeling Through Preservation of Mitochondrial Function and Calcium Handling.JACC. Basic to translational science · 2025Article
- Adenosine triphosphate-induced cell death in heart failure: Is there a link?World journal of cardiology · 2025Review
- Nicotinamide mononucleotide protects septic hearts in mice via preventing cyclophilin F modification and lysosomal dysfunction.Acta pharmacologica Sinica · 2025Article
- The Role of P53 in Myocardial Ischemia-Reperfusion Injury.Cardiovascular drugs and therapy · 2025Review
- Reducing mitochondrial dysfunction through combination therapy to limit ischemia-reperfusion injury in male DCD rats.Frontiers in cardiovascular medicine · 2025Article
- N-terminal cleavage of cyclophilin D boosts its ability to bind F-ATP synthase.Communications biology · 2024Article
- Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.American journal of physiology. Heart and circulatory physiology · 2024Article
- Acute endoplasmic reticulum stress-induced mitochondria respiratory chain damage: The role of activated calpains.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- The Cellular and Organismal Effects of Nitroxides and Nitroxide-Containing Nanoparticles.International journal of molecular sciences · 2024Review
- Landscape of molecular crosstalk between SARS-CoV-2 infection and cardiovascular diseases: emphasis on mitochondrial dysfunction and immune-inflammation.Journal of translational medicine · 2023Article
- Nicotinamide mononucleotide as a therapeutic agent to alleviate multi-organ failure in sepsis.Journal of translational medicine · 2023Article
- Sustained over-expression of calpain-2 induces age-dependent dilated cardiomyopathy in mice through aberrant autophagy.Acta pharmacologica Sinica · 2022Article
- Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria.Life (Basel, Switzerland) · 2022Article
- Inhibition of calpain reduces cell apoptosis by suppressing mitochondrial fission in acute viral myocarditis.Cell biology and toxicology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 8 institutions in 3 countries.
Funding
Abstract
We and others have reported that calpain-1 was increased in myocardial mitochondria from various animal models of heart disease. This study investigated whether constitutive up-regulation of calpain-1 restricted to mitochondria induced myocardial injury and heart failure and, if so, whether these phenotypes could be rescued by selective inhibition of mitochondrial superoxide production. Transgenic mice with human CAPN1 up-regulation restricted to mitochondria in cardiomyocytes (Tg-mtCapn1/tTA) were generated and characterized with low and high over-expression of transgenic human CAPN1 restricted to mitochondria, respectively. Transgenic up-regulation of mitochondria-targeted CAPN1 dose-dependently induced cardiac cell death, adverse myocardial remodeling, heart failure, and early death in mice, the changes of which were associated with mitochondrial dysfunction and mitochondrial superoxide generation. Importantly, a daily injection of mitochondria-targeted superoxide dismutase mimetics mito-TEMPO for 1 month starting from age 2 months attenuated cardiac cell death, adverse myocardial remodeling and heart failure, and reduced mortality in Tg-mtCapn1/tTA mice. In contrast, administration of TEMPO did not achieve similar cardiac protection in transgenic mice. Furthermore, transgenic up-regulation of mitochondria-targeted CAPN1 induced a reduction of ATP5A1 protein and ATP synthase activity in hearts. In cultured cardiomyocytes, increased calpain-1 in mitochondria promoted mitochondrial permeability transition pore (mPTP) opening and induced cell death, which were prevented by over-expression of ATP5A1, mito-TEMPO or cyclosporin A, an inhibitor of mPTP opening. In conclusion, this study has provided direct evidence demonstrating that increased mitochondrial calpain-1 is an important mechanism contributing to myocardial injury and heart failure by disrupting ATP synthase, and promoting mitochondrial superoxide generation and mPTP opening.
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Registered trials
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.