ArticleAging cell2023
DNA repair in cardiomyocytes is critical for maintaining cardiac function in mice.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Viral Myocarditis as a Factor Leading to the Development of Heart Failure Symptoms, Including the Role of Parvovirus B19 Infection-Systematic Review.International journal of molecular sciences · 2024Pooled it
- Interaction between Regulated Cell Death Pathways and Core Cellular Processes: Unraveling the Molecular Mechanisms of Cardiotoxicity of Antitumor Drugs.Current treatment options in oncology · 2026Review
- Integrative transcriptomic and machine learning approach reveals key DDR genes and predictors of ami risk in the Bangladeshi population.Scientific reports · 2026Article
- Plasma protein profiles in different heart failure phenotypes.ESC heart failure · 2026Article
- DNA damage and repair in cardiomyopathy: mechanisms and therapeutic opportunities.American journal of physiology. Heart and circulatory physiology · 2026Review
- Repair and regeneration across the lifespan: an ontogenetic perspective.Frontiers in aging · 2026Review
- Neurocardiac consequences of traumatic brain injury: integrating neuroimmune, autonomic, and cerebrovascular mechanisms.Frontiers in immunology · 2026Review
- The Pathogenic Role of the DNA Double-Stranded Breaks in Hereditary Cardiomyopathies.Heart failure clinics · 2026Review
- Colchicine Alleviates Non-Atherosclerotic Vascular Aging by Targeting Endothelial Dysfunction and Inflammatory Status.Journal of inflammation research · 2026Article
- MoMkt1, a member of XPG/RAD2 nuclease family, regulates development and pathogenicity inVirulence · 2025Article
- DNA double-stranded breaks, a hallmark of aging, defined at the nucleotide resolution, are increased and associated with transcription in the cardiac myocytes in LMNA-cardiomyopathy.Cardiovascular research · 2025Article
- Obesity accelerates cardiovascular ageing.European heart journal · 2025Review
- Causes and consequences of DNA double-stranded breaks in cardiovascular disease.Molecular and cellular biochemistry · 2025Review
- Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction.Cell death & disease · 2025Article
- Hybrid Molecular and Functional Micro-CT Imaging Reveals Increased Myocardial Apoptosis Preceding Cardiac Failure in Progeroid Ercc1 Mice.Molecular imaging and biology · 2024Article
- Replication-Independent ICL Repair: From Chemotherapy to Cell Homeostasis.Journal of molecular biology · 2024Review
- Ercc1 DNA repair deficiency results in vascular aging characterized by VSMC phenotype switching, ECM remodeling, and an increased stress response.Aging cell · 2024Article
- Impact of diffused versus vasculature targeted DNA damage on the heart of mice depleted of telomeric factor Ft1.Aging cell · 2023Article
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Corrections and comments
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Authors and funding
31 authors at 8 institutions in 4 countries.
Funding
Abstract
Heart failure has reached epidemic proportions in a progressively ageing population. The molecular mechanisms underlying heart failure remain elusive, but evidence indicates that DNA damage is enhanced in failing hearts. Here, we tested the hypothesis that endogenous DNA repair in cardiomyocytes is critical for maintaining normal cardiac function, so that perturbed repair of spontaneous DNA damage drives early onset of heart failure. To increase the burden of spontaneous DNA damage, we knocked out the DNA repair endonucleases xeroderma pigmentosum complementation group G (XPG) and excision repair cross-complementation group 1 (ERCC1), either systemically or cardiomyocyte-restricted, and studied the effects on cardiac function and structure. Loss of DNA repair permitted normal heart development but subsequently caused progressive deterioration of cardiac function, resulting in overt congestive heart failure and premature death within 6 months. Cardiac biopsies revealed increased oxidative stress associated with increased fibrosis and apoptosis. Moreover, gene set enrichment analysis showed enrichment of pathways associated with impaired DNA repair and apoptosis, and identified TP53 as one of the top active upstream transcription regulators. In support of the observed cardiac phenotype in mutant mice, several genetic variants in the ERCC1 and XPG gene in human GWAS data were found to be associated with cardiac remodelling and dysfunction. In conclusion, unrepaired spontaneous DNA damage in differentiated cardiomyocytes drives early onset of cardiac failure. These observations implicate DNA damage as a potential novel therapeutic target and highlight systemic and cardiomyocyte-restricted DNA repair-deficient mouse mutants as bona fide models of heart failure.
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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.