ArticleBasic research in cardiology2021
Fibroblast GATA-4 and GATA-6 promote myocardial adaptation to pressure overload by enhancing cardiac angiogenesis.
Article in Basic research in cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- Atorvastatin Attenuates Human Cardiac Fibroblast Activation, with Associated Changes in GATA4/MEF2C and Selected Fibrosis-Related microRNAs.International journal of molecular sciences · 2026Article
- Immunohistochemical detection of putative pathogenetic factors in adhesions of infants: a pilot study.European journal of histochemistry : EJH · 2026Article
- Migration of Cardiac Cells: Hot Topics that have not Attracted Clinical Attention.International journal of medical sciences · 2026Review
- A biodegradable, microstructured, electroconductive and nano-integrated drug eluting patch (MENDEP) for myocardial tissue engineering.Bioactive materials · 2025Article
- Single-cell transcriptomic profiling of heart reveals ANGPTL4 linking fibroblasts and angiogenesis in heart failure with preserved ejection fraction.Journal of advanced research · 2025Article
- Recent Insights into Endogenous Mammalian Cardiac Regeneration Post-Myocardial Infarction.International journal of molecular sciences · 2024Review
- Unraveling the Molecular Mechanisms of SIRT7 in Angiogenesis: Insights from Substrate Clues.International journal of molecular sciences · 2024Review
- Endothelial derived, secreted long non-coding RNAsMolecular therapy. Nucleic acids · 2024Article
- A reduced proteomic signature in critically ill Covid-19 patients determined with plasma antibody micro-array and machine learning.Clinical proteomics · 2024Article
- The SIRT3-ATAD3A axis regulates MAM dynamics and mitochondrial calcium homeostasis in cardiac hypertrophy.International journal of biological sciences · 2024Article
- Inter- and Intracellular Signaling Pathways.Advances in experimental medicine and biology · 2024Review
- MDM2 Regulation of HIF Signaling Causes Microvascular Dysfunction in Hypertrophic Cardiomyopathy.Circulation · 2023Article
- Uncovering the Heterogeneity of Cardiac Lin-KIT+ Cells: A scRNA-seq Study on the Identification of Subpopulations.Stem cells (Dayton, Ohio) · 2023Article
- How does NFAT3 regulate the occurrence of cardiac hypertrophy?International journal of cardiology. Heart & vasculature · 2023Review
- Semaphorin3A Exacerbates Cardiac Microvascular Rarefaction in Pressure Overload-Induced Heart Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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- GATA6 regulates anti-angiogenic properties in human cardiac fibroblasts via modulating LYPD1 expression.Regenerative therapy · 2023Article
- Single-cell RNA sequencing to identify cellular heterogeneity and targets in cardiovascular diseases: from bench to bedside.Basic research in cardiology · 2023Review
- Editorial: Transcription factors in cardiovascular development and remodeling.Frontiers in cell and developmental biology · 2023Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
Heart failure due to high blood pressure or ischemic injury remains a major problem for millions of patients worldwide. Despite enormous advances in deciphering the molecular mechanisms underlying heart failure progression, the cell-type specific adaptations and especially intercellular signaling remain poorly understood. Cardiac fibroblasts express high levels of cardiogenic transcription factors such as GATA-4 and GATA-6, but their role in fibroblasts during stress is not known. Here, we show that fibroblast GATA-4 and GATA-6 promote adaptive remodeling in pressure overload induced cardiac hypertrophy. Using a mouse model with specific single or double deletion of Gata4 and Gata6 in stress activated fibroblasts, we found a reduced myocardial capillarization in mice with Gata4/6 double deletion following pressure overload, while single deletion of Gata4 or Gata6 had no effect. Importantly, we confirmed the reduced angiogenic response using an in vitro co-culture system with Gata4/6 deleted cardiac fibroblasts and endothelial cells. A comprehensive RNA-sequencing analysis revealed an upregulation of anti-angiogenic genes upon Gata4/6 deletion in fibroblasts, and siRNA mediated downregulation of these genes restored endothelial cell growth. In conclusion, we identified a novel role for the cardiogenic transcription factors GATA-4 and GATA-6 in heart fibroblasts, where both proteins act in concert to promote myocardial capillarization and heart function by directing intercellular crosstalk.
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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.