ArticleJournal of the American College of Cardiology2015
Cofilin-2 phosphorylation and sequestration in myocardial aggregates: novel pathogenetic mechanisms for idiopathic dilated cardiomyopathy.
Article in Journal of the American College of Cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- The Heart of the Alzheimer's: A Mindful View of Heart Disease.Frontiers in physiology · 2020Pooled it
- Effects of Cardiomyopathic Mutations on the Cytoplasmic Tropomyosin Isoform Tpm1.7.Molecules (Basel, Switzerland) · 2026Article
- Global Proteoform Alterations Across Multiple Cellular Compartments Underlie Obstructive Hypertrophic Cardiomyopathy.Circulation. Heart failure · 2025Article
- Exploring the Diagnostic Utility of Serum Cofilin-1 and 2 Levels in Patients with Acute Coronary Syndrome: A Case-Control Pilot Study.Indian journal of clinical biochemistry : IJCB · 2025Article
- Mitochondrial connection to Alzheimer's disease and heart failure.Current opinion in physiology · 2025Article
- Particulate matter and co-occurring genetic risk induce oxidative stress and cardiac and brain Alzheimer's pathology.Communications biology · 2025Article
- Alterations in the inflammatory homeostasis of aging-related cardiac dysfunction and Alzheimer's diseases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Plasma exosomal miR-142-3p induced by acupuncture protects against heart injury in rats with myocardial infarction by targeting Cofilin 2.Iranian journal of basic medical sciences · 2025Article
- Is the Relationship Between Cardiovascular Disease and Alzheimer's Disease Genetic? A Scoping Review.Genes · 2024Article
- Data-Independent Acquisition Proteomics and N-Terminomics Methods Reveal Alterations in Mitochondrial Function and Metabolism in Ischemic-Reperfused Hearts.Journal of proteome research · 2024Article
- LIM kinases in cardiovascular health and disease.Frontiers in physiology · 2024Review
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Big tau aggregation disrupts microtubule tyrosination and causes myocardial diastolic dysfunction: from discovery to therapy.European heart journal · 2023Article
- Cerebral amyloid angiopathy-related cardiac injury: Focus on cardiac cell death.Frontiers in cell and developmental biology · 2023Review
- Integrated multi-omics analysis of adverse cardiac remodeling and metabolic inflexibility upon ErbB2 and ERRα deficiency.Communications biology · 2022Article
- Apolipoprotein E Polymorphism, Cardiac Remodeling, and Heart Failure in the ARIC Study.Journal of cardiac failure · 2022Article
- Translation of New and Emerging Therapies for Genetic Cardiomyopathies.JACC. Basic to translational science · 2022Review
- Mitochondrial aldehyde dehydrogenase (ALDH2) rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer's disease via inhibition of ACSL4-dependent ferroptosis.Acta pharmacologica Sinica · 2022Article
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Corrections and comments
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- Erratum issued
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundRecently, tangles and plaque-like aggregates have been identified in certain cases of dilated cardiomyopathy (DCM), traditionally labeled idiopathic (iDCM), where there is no specific diagnostic test or targeted therapy. This suggests a potential underlying cause for some of the iDCM cases. [Corrected]
objectivesThis study sought to identify the make-up of myocardial aggregates to understand the molecular mechanisms of these cases of DCM; this strategy has been central to understanding Alzheimer's disease.
methodsAggregates were extracted from human iDCM samples with high congophilic reactivity (an indication of plaque presence), and the findings were validated in a larger cohort of samples. We tested the expression, distribution, and activity of cofilin in human tissue and generated a cardiac-specific knockout mouse model to investigate the functional impact of the human findings. We also modeled cofilin inactivity in vitro by using pharmacological and genetic gain- and loss-of-function approaches.
resultsAggregates in human myocardium were enriched for cofilin-2, an actin-depolymerizing protein known to participate in neurodegenerative diseases and nemaline myopathy. Cofilin-2 was predominantly phosphorylated, rendering it inactive. Cardiac-specific haploinsufficiency of cofilin-2 in mice recapitulated the human disease's morphological, functional, and structural phenotype. Pharmacological stimulation of cofilin-2 phosphorylation and genetic overexpression of the phosphomimetic protein promoted the accumulation of "stress-like" fibers and severely impaired cardiomyocyte contractility.
conclusionsOur study provides the first biochemical characterization of prefibrillar myocardial aggregates in humans and the first report to link cofilin-2 to cardiomyopathy. The findings suggest a common pathogenetic mechanism connecting certain iDCMs and other chronic degenerative diseases, laying the groundwork for new therapeutic strategies.
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