Basic research in cardiology, 2021-12, Vol.116 (1), p.26-26, Article 26
2021
Details
- Autor(en) / Beteiligte
- Titel
- Fibroblast GATA-4 and GATA-6 promote myocardial adaptation to pressure overload by enhancing cardiac angiogenesis
- Ist Teil von
- Basic research in cardiology, 2021-12, Vol.116 (1), p.26-26, Article 26
- Ort / Verlag
- Berlin/Heidelberg: Springer Berlin Heidelberg
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- SpringerLink
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0300-8428eISSN: 1435-1803DOI: 10.1007/s00395-021-00862-yTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8055639
- Format
- –
- Schlagworte
- Adaptation, Analysis, Angiogenesis, Angiogenic Proteins - genetics, Angiogenic Proteins - metabolism, Animals, Antiangiogenics, Aorta - physiopathology, Aorta - surgery, Arterial Pressure, Blood pressure, Cardiology, Cardiomegaly - etiology, Cardiomegaly - genetics, Cardiomegaly - metabolism, Cardiomegaly - physiopathology, Cell Communication, Cell culture, Cells, Cultured, Congestive heart failure, Constriction, Crosstalk, Deletion, Developmental biology, Disease Models, Animal, DNA binding proteins, Endothelial cells, Endothelium, Epithelial Cells - metabolism, Fibroblasts, Fibroblasts - metabolism, Fibroblasts - pathology, GATA4 Transcription Factor - genetics, GATA4 Transcription Factor - metabolism, GATA6 Transcription Factor - genetics, GATA6 Transcription Factor - metabolism, Gene sequencing, Genes, Genomics, Heart, Heart failure, Heart Failure - etiology, Heart Failure - genetics, Heart Failure - metabolism, Heart Failure - physiopathology, Heart function, Humans, Hypertension, Hypertrophy, Ischemia, Medicine, Medicine & Public Health, Mice, Mice, Knockout, Microvascular Density, Molecular modelling, Myocardium - metabolism, Myocardium - pathology, Neovascularization, Physiologic, Original Contribution, Overloading, Physiological aspects, Sequence analysis, Signal Transduction, siRNA, Transcription factors, Ventricular Remodeling