2024-03-28T19:38:16Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/114622023-10-06T08:58:51Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
00925njm 22002777a 4500
dc
Gonzalez-Hernandez, Sara
author
Gomez, Manuel J
author
Sanchez-Cabo, Fatima
author
Mendez-Ferrer, Simon
author
Munoz-Canoves, Pura
author
Isern, Joan
author
2020-11-06
The molecular mechanisms underlying the formation of coronary arteries during development and during cardiac neovascularization after injury are poorly understood. However, a detailed description of the relevant signaling pathways and functional TFs (transcription factors) regulating these processes is still incomplete.
The goal of this study is to identify novel cardiac transcriptional mechanisms of coronary angiogenesis and vessel remodeling by defining the molecular signatures of coronary vascular endothelial cells during these complex processes.
We demonstrate that Nes-gfp and Nes-CreER
T2
transgenic mouse lines are novel tools for studying the emergence of coronary endothelium and targeting sprouting coronary vessels (but not ventricular endocardium) during development. Furthermore, we identify Sox17 as a critical TF upregulated during the sprouting and remodeling of coronary vessels, visualized by a specific neural enhancer from the Nestin gene that is strongly induced in developing arterioles. Functionally, genetic-inducible endothelial deletion of Sox17 causes deficient cardiac remodeling of coronary vessels, resulting in improper coronary artery formation.
We demonstrated that Sox17 TF regulates the transcriptional activation of Nestin's enhancer in developing coronary vessels while its genetic deletion leads to inadequate coronary artery formation. These findings identify Sox17 as a critical regulator for the remodeling of coronary vessels in the developing heart.
Circ Res. 2020; 127(11):e252-270
0009-7330
http://hdl.handle.net/20.500.12105/11462
32921258
10.1161/CIRCRESAHA.120.317121
Circulation research
Sox17 Controls Emergence and Remodeling of Nestin-Expressing Coronary Vessels.