Evidence map›Paper›PMID 36799218›Full record

ArticleCirculation research2023

Systemic Hypoxemia Induces Cardiomyocyte Hypertrophy and Right Ventricular Specific Induction of Proliferation.

Jaslyn Johnson, Yijun Yang, Zilin Bian, Giana Schena, Yijia Li, Xiaoying Zhang, Deborah M Eaton, Polina Gross, Alexandra Angheloiu, Arshadullah Shaik and 6 more

Abstract read
In one paragraph

Article in Circulation research, 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.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. A Cross-Species and Sex-Specific Meta-Analysis of Transcriptomic Studies of Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2025
    Pooled it
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  15. [Mechanism of IL-17 Signaling Pathway in Spleen Inflammatory Response Induced by Altitude Hypoxia in Mice].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024
    Article
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  19. Developmental Aspects of Cardiac Adaptation to Increased Workload.Journal of cardiovascular development and disease · 2023
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Jaslyn JohnsonIndependence Blue Cross Cardiovascular Research Center (J.J., Y.Y., Y.L., P.G., R.B., H.K., S.M., S.R.H.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Yijun YangIndependence Blue Cross Cardiovascular Research Center (J.J., Y.Y., Y.L., P.G., R.B., H.K., S.M., S.R.H.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0000-0002-6971-2503
Zilin BianTandon School of Engineering, New York University, Brooklyn, NY (Z.B.).ORCID 0000-0003-3514-9369
Giana SchenaRajant Health Inc., Malvern, PA (G.S.).
Yijia LiIndependence Blue Cross Cardiovascular Research Center (J.J., Y.Y., Y.L., P.G., R.B., H.K., S.M., S.R.H.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Xiaoying ZhangDepartment of Cardiovascular Sciences, Center for Translational Medicine (X.Z., Y.T.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Deborah M EatonPenn Cardiovascular Institute, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (D.M.E.).ORCID 0000-0002-6913-7668
Polina GrossIndependence Blue Cross Cardiovascular Research Center (J.J., Y.Y., Y.L., P.G., R.B., H.K., S.M., S.R.H.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Alexandra AngheloiuTemple University, Philadelphia, PA (A.A., A.S., M.F.).
Arshadullah ShaikTemple University, Philadelphia, PA (A.A., A.S., M.F.).ORCID 0000-0002-9670-3944
Michael FosterTemple University, Philadelphia, PA (A.A., A.S., M.F.).
Remus BerrettaIndependence Blue Cross Cardiovascular Research Center (J.J., Y.Y., Y.L., P.G., R.B., H.K., S.M., S.R.H.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Hajime KuboIndependence Blue Cross Cardiovascular Research Center (J.J., Y.Y., Y.L., P.G., R.B., H.K., S.M., S.R.H.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Sadia MohsinIndependence Blue Cross Cardiovascular Research Center (J.J., Y.Y., Y.L., P.G., R.B., H.K., S.M., S.R.H.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Ying TianDepartment of Cardiovascular Sciences, Center for Translational Medicine (X.Z., Y.T.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Steven R HouserIndependence Blue Cross Cardiovascular Research Center (J.J., Y.Y., Y.L., P.G., R.B., H.K., S.M., S.R.H.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0000-0001-6359-5425

Funding

Paracrine hypothesis underlying cardiac stem cell therapyR01HL132391 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI HOUSER, STEVEN R, MOLKENTIN, JEFFERY D · 2016 to 2019
$3.1M
Cortical Bone Stem Cell Therapy for the Infarcted HeartR01HL139960 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI HOUSER, STEVEN R · 2018 to 2021
$2.5M
Regulation of alveolar epithelial regeneration by T cellsR01HL150587 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KOSMIDER, BEATA, TIAN, YING · 2020 to 2023
$2.2M
Paracrine Modulation of Cardiac Repair processes by Cortical Bone Derived Stem CellsR01HL137850 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI MOHSIN, SADIA · 2018 to 2021
$1.6M
Paracrine Modulation of Cardiac Repairprocesses by Cortical Bone Derived Stem CellsR56HL137850 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI MOHSIN, SADIA · 2017 to 2017
$396k
Exosomes secreted by Cortical Bone Stem Cells mediate Cardiac RepairF31HL143865 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI JOHNSON, JASLYN · 2018 to 2020
$92k
NHLBI NIH HHS F31 HL143865NHLBI NIH HHS R01 HL132391NHLBI NIH HHS R01 HL137850NHLBI NIH HHS R01 HL139960NHLBI NIH HHS R01 HL150587NHLBI NIH HHS R56 HL137850
6 · The paper itself

Abstract

backgroundA recent study suggests that systemic hypoxemia in adult male mice can induce cardiac myocytes to proliferate. The goal of the present experiments was to confirm these results, provide new insights on the mechanisms that induce adult cardiomyocyte cell cycle reentry, and to determine if hypoxemia also induces cardiomyocyte proliferation in female mice.

methodsEdU-containing mini pumps were implanted in 3-month-old, male and female C57BL/6 mice. Mice were placed in a hypoxia chamber, and the oxygen was lowered by 1% every day for 14 days to reach 7% oxygen. The animals remained in 7% oxygen for 2 weeks before terminal studies. Myocyte proliferation was also studied with a mosaic analysis with double markers mouse model.

resultsHypoxia induced cardiac hypertrophy in both left ventricular (LV) and right ventricular (RV) myocytes, with LV myocytes lengthening and RV myocytes widening and lengthening. Hypoxia induced an increase (0.01±0.01% in normoxia to 0.11±0.09% in hypoxia) in the number of EdU+ RV cardiomyocytes, with no effect on LV myocytes in male C57BL/6 mice. Similar results were observed in female mice. Furthermore, in mosaic analysis with double markers mice, hypoxia induced a significant increase in RV myocyte proliferation (0.03±0.03% in normoxia to 0.32±0.15% in hypoxia of RFP+ myocytes), with no significant change in LV myocyte proliferation. RNA sequencing showed upregulation of mitotic cell cycle genes and a downregulation of Cullin genes, which promote the G1 to S phase transition in hypoxic mice. There was significant proliferation of nonmyocytes and mild cardiac fibrosis in hypoxic mice that did not disrupt cardiac function. Male and female mice exhibited similar gene expression following hypoxia.

conclusionsSystemic hypoxia induces a global hypertrophic stress response that was associated with increased RV proliferation, and while LV myocytes did not show increased proliferation, our results minimally confirm previous reports that hypoxia can induce cardiomyocyte cell cycle activity in vivo.

Indexed as

HypoxiaMyocytes, CardiacAnimalsCell ProliferationFemaleHypertrophyMaleMiceMice, Inbred C57BLOxygenOxygencell proliferationcytokinesishypoxiamyocytes, cardiacneovascularization, pathologicventricular remodeling

Identifiers

PMID36799218
PMCPMC10023496

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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.