ArticleCirculation2022
Transient Cell Cycle Induction in Cardiomyocytes to Treat Subacute Ischemic Heart Failure.
Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 63 citations in OpenAlex.
- Maternal Exercise and Offspring Cardiac Regenerative Potential: Roles of Apelin and α-Ketoglutarate.Biology · 2026Review
- Small-molecule cocktail 2SM promotes heart regeneration via inducing embryonic-like cardiomyocyte state.Cell regeneration (London, England) · 2026Article
- Cardiac immunity and heart repair: Mechanism, challenge, and future direction.Chinese medical journal · 2026Review
- Epigenetic Control of Mammalian Cardiomyocyte Proliferation.Current cardiology reports · 2026Review
- Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- CRISPR-Cas-based activation of PPARGC1A boosts endogenous mitochondria and enhances cardiac function after myocardial infarction.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Identification of myocardial contractility-related genes as regenerative targets and diagnostic biomarkers in coronary artery disease.Regenerative therapy · 2026Article
- Mechanisms and Therapeutic Potential of Human Cardiomyocyte Proliferation.Journal of cardiovascular development and disease · 2026Review
- Cullin-associated and neddylation-dissociated protein 1 (CAND1) promotes cardiomyocyte proliferation and heart regeneration by enhancing the ubiquitinated degradation of Mps one binder kinase activator 1b (Mob1b).Cell death and differentiation · 2025Article
- Cardiomyocyte maturation and proliferation is a flip coin.BMC cardiovascular disorders · 2025Review
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Rewiring cell identity and metabolism to drive cardiomyocyte proliferation.Cell regeneration (London, England) · 2025Review
- Identification of Biomarkers for Acute Myocardial Infarction Based on Cell Senescence Genes and Machine Learning.Anatolian journal of cardiology · 2025Article
- Cardiomyocyte regeneration after infarction: changes, opportunities and challenges.Molecular and cellular biochemistry · 2025Review
- A new model of heart failure with preserved ejection fraction induced by metabolic syndrome in Ossabaw miniature swine.Basic research in cardiology · 2025Article
- LncRNA SNHG15 promotes angiogenesis and improves cardiac repair after myocardial infarction through MiR-665-mediated KDR expression.Cellular and molecular life sciences : CMLS · 2025Article
- Cardiac rehabilitation in porcine models: Advances in therapeutic strategies for ischemic heart disease.Zoological research · 2025Review
- Identification and Functional Validation ofGenes · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity.NPJ Regenerative medicine · 2025Article
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26 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundThe regenerative capacity of the heart after myocardial infarction is limited. Our previous study showed that ectopic introduction of 4 cell cycle factors (4F; CDK1 [cyclin-dependent kinase 1], CDK4 [cyclin-dependent kinase 4], CCNB [cyclin B1], and CCND [cyclin D1]) promotes cardiomyocyte proliferation in 15% to 20% of infected cardiomyocytes in vitro and in vivo and improves cardiac function after myocardial infarction in mice.
methodsUsing temporal single-cell RNA sequencing, we aimed to identify the necessary reprogramming stages during the forced cardiomyocyte proliferation with 4F on a single cell basis. Using rat and pig models of ischemic heart failure, we aimed to start the first preclinical testing to introduce 4F gene therapy as a candidate for the treatment of ischemia-induced heart failure.
resultsTemporal bulk and single-cell RNA sequencing and further biochemical validations of mature human induced pluripotent stem cell-derived cardiomyocytes treated with either LacZ or 4F adenoviruses revealed full cell cycle reprogramming in 15% of the cardiomyocyte population at 48 hours after infection with 4F, which was associated mainly with sarcomere disassembly and metabolic reprogramming (n=3/time point/group). Transient overexpression of 4F, specifically in cardiomyocytes, was achieved using a polycistronic nonintegrating lentivirus (NIL) encoding 4F; each is driven by a TNNT2 (cardiac troponin T isoform 2) promoter (TNNT2-4Fpolycistronic-NIL). TNNT2-4Fpolycistronic-NIL or control virus was injected intramyocardially 1 week after myocardial infarction in rats (n=10/group) or pigs (n=6-7/group). Four weeks after injection, TNNT2-4Fpolycistronic-NIL-treated animals showed significant improvement in left ventricular ejection fraction and scar size compared with the control virus-treated animals. At 4 months after treatment, rats that received TNNT2-4Fpolycistronic-NIL still showed a sustained improvement in cardiac function and no obvious development of cardiac arrhythmias or systemic tumorigenesis (n=10/group).
conclusionsThis study provides mechanistic insights into the process of forced cardiomyocyte proliferation and advances the clinical feasibility of this approach by minimizing the oncogenic potential of the cell cycle factors owing to the use of a novel transient and cardiomyocyte-specific viral construct.
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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.