ArticleScience translational medicine2019
Control of cytokinesis by β-adrenergic receptors indicates an approach for regulating cardiomyocyte endowment.
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Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
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76 citing papers in PubMed, 113 citations in OpenAlex.
- Myocardial Immune Niches in Homeostasis and Inflammation.Immunological reviews · 2026Review
- Inhibition of Cyclophilin D Rescues Cardiac Function and Bioenergetic Defects Caused by Neonatal Hypoxia.JACC. Basic to translational science · 2026Article
- Neural signaling contributes to heart formation and growth in the invertebrate chordate, Ciona robusta.PLoS biology · 2026Article
- Mechanisms and Therapeutic Potential of Human Cardiomyocyte Proliferation.Journal of cardiovascular development and disease · 2026Review
- Cell-free strategies for cardiomyocyte proliferation and heart repair.Pharmacological reports : PR · 2026Review
- Insights into Cardiomyocyte Regeneration from Screening and Transcriptomics Approaches.International journal of molecular sciences · 2026Review
- Development and modeling of cardiac autonomic innervation.Nature cardiovascular research · 2025Review
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Effectiveness of the continuing care model for improving quality of life, cardiac function and outcomes in patients with coronary heart disease combined with heart failure after percutaneous coronary intervention: A retrospective study.Pakistan journal of medical sciences · 2025Article
- Integrative approaches in cardiac tissue engineering: Bridging cellular complexity to create accurate physiological models.iScience · 2025Review
- Norepinephrine inhibits cell cycle re-entry of neonatal rat ventricular cardiomyocytes characterized by the absence of de novo nestin expression.Physiological reports · 2025Article
- A Case of Complete Functional Myocardial Regeneration in a Human Neonate.JACC. Case reports · 2025Article
- The unique hypertrophic and fibrotic features of neonatal right ventricle in response to pressure overload.Scientific reports · 2025Article
- β-adrenergic receptor inhibits heart regeneration by downregulating Yap m6A modification.Cell death & disease · 2025Article
- Induced Cytokinesis Generates Highly Proliferative Mononuclear Cardiomyocytes at the Expense of Contractility.Circulation · 2025Article
- NestinJournal of cellular physiology · 2025Article
- Molecular and cellular neurocardiology in heart disease.The Journal of physiology · 2025Review
- Dynamic map illuminates Hippo-cMyc module crosstalk driving cardiomyocyte proliferation.Development (Cambridge, England) · 2025Article
- A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease.Circulation · 2025Article
- Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity.NPJ Regenerative medicine · 2025Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
35 authors at 11 institutions in 1 country.
Honghai LiuRichard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.ORCID 0000-0002-0693-6083
Cheng-Hai ZhangDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.ORCID 0000-0002-6759-3782
Niyatie AmmanamanchiRichard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.ORCID 0000-0002-9335-3512
Sangita SureshDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.ORCID 0000-0001-7285-971X
Christopher LewarchikRichard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
Krithika RaoRichard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
Gerrida M UysDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.ORCID 0000-0002-3996-5809
Lu HanRichard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.ORCID 0000-0001-9967-4723
Maryline AbrialDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.ORCID 0000-0002-3001-9840
Dean YimlamaiDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
Balakrishnan GanapathyRichard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
Christelle GuillermierDivision of Genetics and Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
Nathalie ChenRichard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.ORCID 0000-0001-9951-5642
Mugdha KhaladkarDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, 301A/B Lynch Laboratory, 433 S University Avenue, Philadelphia, PA 19104, USA.ORCID 0000-0002-5152-4694
Jennifer SpaethlingDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
James H EberwineDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-9363-0858
Junhyong KimDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, 301A/B Lynch Laboratory, 433 S University Avenue, Philadelphia, PA 19104, USA.ORCID 0000-0002-7726-8246
Stuart WalshDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.
Sangita ChoudhuryDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.
Kathryn LittleRichard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
Kimberly FrancisRichard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
Mahesh SharmaDivision of Cardiothoracic Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Melita ViegasPediatric Cardiothoracic Surgery, UPMC Children's Hospital of Pittsburgh and Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA 15224, USA.ORCID 0000-0001-5155-2153
Abha BaisDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.ORCID 0000-0001-5910-1306
Dennis KostkaDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.ORCID 0000-0002-1460-5487
Jun DingComputational Biology Department and Machine Learning Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Ziv Bar-JosephComputational Biology Department and Machine Learning Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0003-3430-6051
Yijen WuDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.ORCID 0000-0001-9509-5417
Vijay YechoorDiabetes and Beta Cell Biology Center, Division of Endocrinology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15238, USA.ORCID 0000-0002-9981-6784
Mousumi MoulikDivision of Cardiology, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
Jennifer JohnsonDivision of Cardiology, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
Jacqueline WeinbergDivision of Cardiology, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.ORCID 0000-0002-1644-8649
Miguel Reyes-MúgicaDivision of Pediatric Pathology, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.ORCID 0000-0001-5698-3702
Matthew L SteinhauserDivision of Genetics and Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
Bernhard KühnRichard King Mellon Foundation Institute for Pediatric Research and Division of Cardiology, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA. bernhard.kuhn2@chp.edu.ORCID 0000-0002-1855-7072
Richard King Mellon Foundation · USBoston Children's Hospital · USUniversity of Pittsburgh · USChildren's Hospital of Pittsburgh · USBrigham and Women's Hospital · USCarnegie Mellon University · USTranslational Therapeutics (United States) · USUniversity of Pennsylvania · USCalifornia Institute for Regenerative Medicine · USMagee-Womens Hospital · USUniversity of North Carolina at Chapel Hill · US
Funding
VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0MUniversity of Pittsburgh Clinical and Translational Science InstituteUL1TR001857 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2016 to 2025
$129.3MRole of Single Cell mRNA Variation in Systems Associated Electrically Excitable CU01MH098953 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI EBERWINE, JAMES H, KIM, JUNHYONG · 2012 to 2016
$11.4MMyofibril disassembly during neonatal heart muscle cell proliferationR01HL106302 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KUHN, BERNHARD · 2011 to 2015
$2.1MBLRD VA I01 BX002678NCATS NIH HHS UL1 TR001857NCI NIH HHS P30 CA047904NHLBI NIH HHS R01 HL106302NIMH NIH HHS U01 MH098953
Abstract
One million patients with congenital heart disease (CHD) live in the United States. They have a lifelong risk of developing heart failure. Current concepts do not sufficiently address mechanisms of heart failure development specifically for these patients. Here, analysis of heart tissue from an infant with tetralogy of Fallot with pulmonary stenosis (ToF/PS) labeled with isotope-tagged thymidine demonstrated that cardiomyocyte cytokinesis failure is increased in this common form of CHD. We used single-cell transcriptional profiling to discover that the underlying mechanism of cytokinesis failure is repression of the cytokinesis gene ECT2, downstream of β-adrenergic receptors (β-ARs). Inactivation of the β-AR genes and administration of the β-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the number of cardiomyocytes (endowment) and conferred benefit after myocardial infarction in adults. Propranolol enabled the division of ToF/PS cardiomyocytes in vitro. These results suggest that β-blockers could be evaluated for increasing cardiomyocyte division in patients with ToF/PS and other types of CHD.
Indexed as
Adrenergic beta-AntagonistsAnimalsAnimals, NewbornCell ProliferationCytokinesisHumansMiceMyocytes, CardiacPropranololProto-Oncogene ProteinsRatsReceptors, Adrenergic, betaAdrenergic beta-AntagonistsECT2 protein, humanPropranololProto-Oncogene ProteinsReceptors, Adrenergic, beta
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