ArticleJournal of the American Heart Association2019
Inhibition of Senescence-Associated Genes Rb1 and Meis2 in Adult Cardiomyocytes Results in Cell Cycle Reentry and Cardiac Repair Post-Myocardial Infarction.
Article in Journal of the American Heart Association, 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, 69 citations in OpenAlex.
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Review
- Cell-free strategies for cardiomyocyte proliferation and heart repair.Pharmacological reports : PR · 2026Review
- Cellular Senescence, Inflammaging and Cardiovascular Disease.Immunological reviews · 2026Review
- Enhancing cardiomyocyte reprogramming efficiency by targeting cellular senescence is mediated via Rb1 gene.Stem cell research & therapy · 2025Article
- Cellular senescence and cell therapy in cardiovascular diseases.Stem cell research & therapy · 2025Review
- A Multiomics Approach to Defining Target-Organ Injury in Youths With Primary Hypertension: The SHIP AHOY Cohort.Journal of the American Heart Association · 2025Article
- Inflammaging and Senescence-Driven Extracellular Matrix Remodeling in Age-Associated Cardiovascular Disease.Biomolecules · 2025Review
- Biomaterial-Based Nucleic Acid Delivery Systems for In Situ Tissue Engineering and Regenerative Medicine.International journal of molecular sciences · 2025Review
- The context-dependent effect of cellular senescence: From embryogenesis and wound healing to aging.Ageing research reviews · 2025Review
- Article
- Mechanisms of aging in the cardiovascular system: challenges and opportunities.Frontiers in immunology · 2025Review
- A Multi-Omics Approach to Defining Target Organ Injury in Youth with Primary Hypertension.bioRxiv : the preprint server for biology · 2024Article
- Targeting cardiomyocyte cell cycle regulation in heart failure.Basic research in cardiology · 2024Review
- Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets.Cell death discovery · 2024Review
- Mechanistic insights into cardiac regeneration and protection through MEIS inhibition.Turkish journal of biology = Turk biyoloji dergisi · 2024Article
- End binding-3 inhibitor activates regenerative program in age-related macular degeneration.Cell reports. Medicine · 2023Article
- Comparative Analysis of Heart Regeneration: Searching for the Key to Heal the Heart-Part II: Molecular Mechanisms of Cardiac Regeneration.Journal of cardiovascular development and disease · 2023Review
- Harnessing developmental cues for cardiomyocyte production.Development (Cambridge, England) · 2023Review
- Non-viral gene delivery to human mesenchymal stem cells: a practical guide towards cell engineering.Journal of biological engineering · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Background Myocardial infarction results in a large-scale cardiomyocyte loss and heart failure due to subsequent pathological remodeling. Whereas zebrafish and neonatal mice have evident cardiomyocyte expansion following injury, adult mammalian cardiomyocytes are principally nonproliferative. Despite historical presumptions of stem cell-mediated cardiac regeneration, numerous recent studies using advanced lineage-tracing methods demonstrated that the only source of cardiomyocyte renewal originates from the extant myocardium; thus, the augmented proliferation of preexisting adult cardiomyocytes remains a leading therapeutic approach toward cardiac regeneration. In the present study we investigate the significance of suppressing cell cycle inhibitors Rb1 and Meis2 to promote adult cardiomyocyte reentry to the cell cycle. Methods and Results In vitro experiments with small interfering RNA-mediated simultaneous knockdown of Rb1 and Meis2 in both adult rat cardiomyocytes, isolated from 12-week-old Fischer rats, and human induced pluripotent stem cell-derived cardiomyocytes showed a significant increase in cell number, a decrease in cell size, and an increase in mononucleated cardiomyocytes. In vivo, a hydrogel-based delivery method for small interfering RNA-mediated silencing of Rb1 and Meis2 is utilized following myocardial infarction. Immunofluorescent imaging analysis revealed a significant increase in proliferation markers 5-ethynyl-2'-deoxyuridine, PH3, KI67, and Aurora B in adult cardiomyocytes as well as improved cell survivability with the additional benefit of enhanced peri-infarct angiogenesis. Together, this intervention resulted in a reduced infarct size and improved cardiac function post-myocardial infarction. Conclusions Silencing of senescence-inducing pathways in adult cardiomyocytes via inhibition of Rb1 and Meis2 results in marked cardiomyocyte proliferation and increased protection of cardiac function in the setting of ischemic injury.
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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.