ArticleProceedings of the National Academy of Sciences of the United States of America2004
Bcl-2 overexpression corrects mitochondrial defects and ameliorates inherited desmin null cardiomyopathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 129 citations in OpenAlex.
- Patient specific regulation of metabolism and cell death pathways in m.3243A>G mutated iPS-cells.Scientific reports · 2026Article
- BAK and BAX: Therapeutic Targets for Acute Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury.Biology · 2025Review
- Common and Key Differential Pathogenic Pathways in Desminopathy and Titinopathy.International journal of medical sciences · 2024Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Myocardial Infarction as a Consequence of Mitochondrial Dysfunction.Current cardiology reviews · 2023Review
- Desmin Knock-Out Cardiomyopathy: A Heart on the Verge of Metabolic Crisis.International journal of molecular sciences · 2022Article
- Skeletal and Cardiac Muscle Disorders Caused by Mutations in Genes Encoding Intermediate Filament Proteins.International journal of molecular sciences · 2021Review
- Aortic acceleration as a noninvasive index of left ventricular contractility in the mouse.Scientific reports · 2021Article
- Bcl-2 Overexpression and Hypoxia Synergistically Enhance Angiogenic Properties of Dental Pulp Stem Cells.International journal of molecular sciences · 2020Article
- Acute petrified myocardium associated with meningococcal sepsis in childhood-onset systemic lupus erythematous: a fatal case.Revista do Instituto de Medicina Tropical de Sao Paulo · 2019Article
- Transcription Factor EB Activation Rescues Advanced αB-Crystallin Mutation-Induced Cardiomyopathy by Normalizing Desmin Localization.Journal of the American Heart Association · 2019Article
- Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins.F1000Research · 2019Review
- Intermediate filaments in cardiomyopathy.Biophysical reviews · 2018Review
- Type III Intermediate Filaments Desmin, Glial Fibrillary Acidic Protein (GFAP), Vimentin, and Peripherin.Cold Spring Harbor perspectives in biology · 2017Review
- Myofibrillar Myopathies: New Perspectives from Animal Models to Potential Therapeutic Approaches.Journal of neuromuscular diseases · 2017Review
- Desmin and αB-crystallin interplay in the maintenance of mitochondrial homeostasis and cardiomyocyte survival.Journal of cell science · 2016Article
- Review
- Desmin enters the nucleus of cardiac stem cells and modulates Nkx2.5 expression by participating in transcription factor complexes that interact with the nkx2.5 gene.Biology open · 2016Article
- Desmin related disease: a matter of cell survival failure.Current opinion in cell biology · 2015Review
- Loss of the eukaryotic initiation factor 2α kinase general control nonderepressible 2 protects mice from pressure overload-induced congestive heart failure without affecting ventricular hypertrophy.Hypertension (Dallas, Tex. : 1979) · 2014Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
One of the hallmarks of cardiomyopathy and heart failure is pronounced and progressive cardiomyocyte death. Understanding the mechanisms involved in cardiomyocyte cell death is a topic of great interest for treatment of cardiac disease. Mice null for desmin, the muscle-specific member of the intermediate filament gene family, develop cardiomyopathy characterized by extensive cardiomyocyte death, fibrosis, calcification, and eventual heart failure. The earliest ultrastructural defects are observed in mitochondria. In the present study, we have demonstrated that these mitochondrial abnormalities are the primary cause of the observed cardiomyopathy and that these defects can be ameliorated by overexpression of bcl-2 in desmin null heart. Overexpression of bcl-2 in the desmin null heart results in correction of mitochondrial defects, reduced occurrence of fibrotic lesions in the myocardium, prevention of cardiac hypertrophy, restoration of cardiomyocyte ultrastructure, and significant improvement of cardiac function. Furthermore, we have found that loss of desmin also diminishes the capacity of mitochondria to resist exposure to calcium, a defect that can be partially restored by bcl-2 overexpression. These results point to a unique function for desmin in protection of mitochondria from calcium exposure that can be partially rescued by overexpression of bcl-2. We show that bcl-2 cardiac overexpression has provided significant improvement of an inherited form of cardiomyopathy, revealing the potential for bcl-2, and perhaps other genes in the family, as therapeutic agents for heart disease of many types, including inherited forms.
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