ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2013
Hypoxia inhibits cardiomyocyte proliferation in fetal rat hearts via upregulating TIMP-4.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- Nuclear Lactate Dehydrogenase A Resists Cardiomyocyte Cell Cycle Arrest Induced by Oxidative Stress.Journal of cardiovascular development and disease · 2025Article
- Enhanced neoangiogenesis and balance of the immune response mediated by the Wilms' tumor suppressor WT1 favor repair after myocardial infarction.Theranostics · 2025Article
- Targeting cardiomyocyte cell cycle regulation in heart failure.Basic research in cardiology · 2024Review
- Cardioprotective Effects of Dexmedetomidine in an Oxidative-Stress In Vitro Model of Neonatal Rat Cardiomyocytes.Antioxidants (Basel, Switzerland) · 2023Article
- Cardiomyocyte Proliferation from Fetal- to Adult- and from Normal- to Hypertrophy and Failing Hearts.Biology · 2022Review
- Silencing RNA for MMPs May Be Utilized for Cardioprotection.Cardiovascular therapeutics · 2022Article
- Changes in Cardiomyocyte Cell Cycle and Hypertrophic Growth During Fetal to Adult in Mammals.Journal of the American Heart Association · 2021Review
- Cardiomyocyte nuclearity and ploidy: when is double trouble?Journal of muscle research and cell motility · 2020Article
- How to Stimulate Myocardial Regeneration in Adult Mammalian Heart: Existing Views and New Approaches.BioMed research international · 2020Review
- Multi-Omics Integration Reveals Short and Long-Term Effects of Gestational Hypoxia on the Heart Development.Cells · 2019Article
- Foetal hypoxia impacts methylome and transcriptome in developmental programming of heart disease.Cardiovascular research · 2019Article
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function.Heart failure reviews · 2017Review
- MicroRNA-210 suppresses glucocorticoid receptor expression in response to hypoxia in fetal rat cardiomyocytes.Oncotarget · 2017Article
- Proteomic Analysis of Endothelin-1 Targets in the Regulation of Cardiomyocyte Proliferation.Current topics in medicinal chemistry · 2017Article
- Dexamethasone Induces Cardiomyocyte Terminal Differentiation via Epigenetic Repression of Cyclin D2 Gene.The Journal of pharmacology and experimental therapeutics · 2016Article
- Hypoxia induces autophagy in cardiomyocytes via a hypoxia-inducible factor 1-dependent mechanism.Experimental and therapeutic medicine · 2016Article
- Irisin Ameliorates Hypoxia/Reoxygenation-Induced Injury through Modulation of Histone Deacetylase 4.PloS one · 2016Article
- HDAC4 degradation mediates HDAC inhibition-induced protective effects against hypoxia/reoxygenation injury.Journal of cellular physiology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Maternal hypoxia inhibits cardiomyocyte proliferation in the heart of fetal and neonatal rats. The present study tested the hypothesis that hypoxia has a direct effect inhibiting cardiomyocyte proliferation via upregulating tissue inhibitors of metalloproteinases (TIMP) in fetal rat hearts. Isolated fetal rat hearts and rat embryonic ventricular myocyte H9c2 cells were treated ex vivo with 20% or 1% O(2) for 48 or 24 h, respectively. Hypoxia caused a significant reduction in cardiomyocyte Ki-67 expression and bromodeoxyuridine incorporation in fetal hearts and H9c2 cells. In both fetal hearts and H9c2 cells, hypoxia resulted in a significant decrease in a cell division marker cyclin D2 but an increase in a cell division inhibitor p27. Additionally, hypoxia caused an upregulation of TIMP-3 and TIMP-4 in fetal hearts and H9c2 cells. Knockdown of TIMP-3 in H9c2 cells significantly increased cyclin D2 and Ki-67 and partially blocked the hypoxia-induced inhibition of cyclin D2 and Ki-67 in H9c2 cells. Unlike TIMP-3, TIMP-4 knockdown had no significant effects on the basal levels of cell proliferation but completely abrogated the hypoxia-mediated effects. These findings provide evidence of a novel causal role of TIMP-4 and TIMP-3 in the direct inhibitory effect of hypoxia on cardiomyocyte proliferation in the developing heart.
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