Sox17 Controls Emergence and Remodeling of Nestin-Expressing Coronary Vessels.
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González-Hernández, S., Gómez, M. J., Sánchez-Cabo, F., Méndez-Ferrer, S., Muñoz-Cánoves, P., & Isern, J. (2020). Sox17 Controls Emergence and Remodeling of Nestin-Expressing Coronary Vessels.. Circulation research, 127 (11), e252-e270. https://doi.org/10.1161/circresaha.120.317121
Rationale: 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 transcription factors regulating these processes is still incomplete. Objective: 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 (EC) during these complex processes. Methods and Results: We demonstrate that Nes-gfp and Nes-CreERT2 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 transcription factor 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. Conclusions: We demonstrated that Sox17 transcription factor 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.
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External DOI: https://doi.org/10.1161/circresaha.120.317121
This record's URL: https://www.repository.cam.ac.uk/handle/1810/311119
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