Loading...
Fibroblast GATA-4 and GATA-6 promote myocardial adaptation to pressure overload by enhancing cardiac angiogenesis.
Dittrich, Gesine M Froese, Natali Wang, Xue Kroeger, Hannah Wang, Honghui Szaroszyk, Malgorzata Malek-Mohammadi, Mona Cordero, Julio Keles, Merve Korf-Klingebiel, Mortimer
Dittrich, Gesine M
Froese, Natali
Wang, Xue
Kroeger, Hannah
Wang, Honghui
Szaroszyk, Malgorzata
Malek-Mohammadi, Mona
Cordero, Julio
Keles, Merve
Korf-Klingebiel, Mortimer
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2021-04-19
Submitted date
Files
Loading...
Open Access publication
Adobe PDF, 7.28 MB
Other Titles
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.
Citation
Basic Res Cardiol. 2021 Apr 19;116(1):26. doi: 10.1007/s00395-021-00862-y.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
EISSN
1435-1803
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution 4.0 International