Evidence map›Paper›PMID 24766806›Full record

ArticleCell2014

The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response.

Bao N Puente, Wataru Kimura, Shalini A Muralidhar, Jesung Moon, James F Amatruda, Kate L Phelps, David Grinsfelder, Beverly A Rothermel, Rui Chen, Joseph A Garcia and 15 more

Erratum issued Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT05632432 (Autologous Atrial Appendage Micrografts Transplanted During Coronary Artery Bypass Surgery), which is not on this map. Cited by 564 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
564citing papers in PubMed, 3 pooled it
21.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05632432 narecruitingnot on this mapstarted 2024, after this paper: background citation

Autologous Atrial Appendage Micrografts Transplanted During Coronary Artery Bypass Surgery: the AAMS2 Randomized, Double-blinded, and Placebo-controlled Trial

TypeinterventionalSponsorHospital District of Helsinki and UusimaaRan2024 to 2026Enrolled50ConditionsIschemic Heart Disease, Ischemic Cardiomyopathy, Heart Failure, Systolic, Heart Failure NYHA Class IIIArmsEpicardial AAMs-patch transplantation, RNA-stabilized whole blood sampling, Plasma sampling, Transthoracic echocardiography, Late-gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRI)
3 · Its place in the literature

Who cites it

564 citing papers in PubMed, 3 syntheses or guidelines pooled it, 876 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Review
  5. Article
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  7. Mechanical regulation of cell memory.Nature structural & molecular biology · 2026
    Review
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  19. Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026
    Review
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504 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 7 institutions in 3 countries.

Bao N PuenteDepartment of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Wataru KimuraDepartment of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Shalini A MuralidharDepartment of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jesung MoonDepartment of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
James F AmatrudaDepartment of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Kate L PhelpsDepartment of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
David GrinsfelderDepartment of Clinical Science, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Beverly A RothermelDepartment of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Rui ChenDepartment of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Joseph A GarciaDepartment of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Celio X SantosCardiovascular Division, King's College London BHF Centre of Research Excellence, School of Medicine, James Black Centre, London SE5 9NU, UK.
SuWannee ThetDepartment of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Eiichiro MoriDepartment of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Michael T KinterFree Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Paul M RindlerFree Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Serena ZacchignaMolecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, 34149 Trieste, Italy.
Shibani MukherjeeDepartment of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
David J ChenDepartment of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Ahmed I MahmoudCardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, MA 02115, USA.
Mauro GiaccaMolecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, 34149 Trieste, Italy.
Peter S RabinovitchDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Asaithamby AroumougameDepartment of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Ajay M ShahDepartment of Clinical Science, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Luke I SzwedaFree Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Hesham A SadekDepartment of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: hesham.sadek@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USOklahoma Medical Research Foundation · USInternational Centre for Genetic Engineering and Biotechnology · ITKing's College London · GBBrigham and Women's Hospital · USSouthwestern Medical Center · USUniversity of Washington · US

Funding

Modulating Calcineurin Signaling Pathways in MuscleR01HL072016 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI ROTHERMEL, BEVERLY A · 2003 to 2012
$3.7M
Role of Meis1 in Regulation of Cardiomyocyte ProliferationR01HL115275 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI SADEK, HESHAM · 2012 to 2016
$2.4M
Calcineurin's role in circadian regulation of cardiac function and remodelingR01HL097768 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI ROTHERMEL, BEVERLY A · 2009 to 2012
$1.6M
Molecular mechanisms dictating Sirt1/HIF-2 signaling during hypoxiaR01HL108104 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI GARCIA, JOSEPH ANTHONY · 2011 to 2014
$1.3M
Dynamic Regulation of Erythropoietin Gene Expression in Mammals.I01BX000446 · VA · VA NORTH TEXAS HEALTH CARE SYSTEM · PI Joseph Anthony Garcia · 2009 to 2026
–
BLRD VA I01 BX000446British Heart Foundation RG/13/11/30384NHLBI NIH HHS 1R01HL115275-01NHLBI NIH HHS R01 HL072016NHLBI NIH HHS R01 HL097768NHLBI NIH HHS R01 HL108104NHLBI NIH HHS R01 HL115275
6 · The paper itself

Abstract

The mammalian heart has a remarkable regenerative capacity for a short period of time after birth, after which the majority of cardiomyocytes permanently exit cell cycle. We sought to determine the primary postnatal event that results in cardiomyocyte cell-cycle arrest. We hypothesized that transition to the oxygen-rich postnatal environment is the upstream signal that results in cell-cycle arrest of cardiomyocytes. Here, we show that reactive oxygen species (ROS), oxidative DNA damage, and DNA damage response (DDR) markers significantly increase in the heart during the first postnatal week. Intriguingly, postnatal hypoxemia, ROS scavenging, or inhibition of DDR all prolong the postnatal proliferative window of cardiomyocytes, whereas hyperoxemia and ROS generators shorten it. These findings uncover a protective mechanism that mediates cardiomyocyte cell-cycle arrest in exchange for utilization of oxygen-dependent aerobic metabolism. Reduction of mitochondrial-dependent oxidative stress should be an important component of cardiomyocyte proliferation-based therapeutic approaches.

Indexed as

Cell Cycle CheckpointsAcetylcysteineAnimalsCell ProliferationDNA DamageFree Radical ScavengersMiceMitochondriaMyocytes, CardiacReactive Oxygen SpeciesZebrafishAcetylcysteineFree Radical ScavengersReactive Oxygen Species

Identifiers

PMID24766806
PMCPMC4104514
OpenAlexW2035847235

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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.