Sox17 Controls Emergence and Remodeling of Nestin-Expressing Coronary Vessels
- 6 November 2020
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 127 (11), E252-E270
- https://doi.org/10.1161/CIRCRESAHA.120.317121
Abstract
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 TFs (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 during these complex processes. Methods and Results: 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. Conclusions: 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.Funding Information
- Ministerio de Economía y Competitividad (BFU2012-35892)
- Ministerio de Ciencia e Innovación (RYC-2011-09209)
- Ministerio de Economía, Industria y Competitividad, Gobierno de España (BES-2013-065514)
- Ministerio de Economía y Competitividad (SAF-2011-30308)
- Ministerio de Ciencia e Innovación (RYC-2009-04703)
- EC | FP7 | FP7 People: Marie-Curie Actions (FP7-PEOPLE-2011-RG-294096)
- Comunidad de Madrid (S2010/BMD-2542)
- Fundació la Marató de TV3 (120/C/2015-20153032)
- Ministerio de Ciencia e Innovación (RTI2018-095497-B-I00)
- Ministerio de Economía, Industria y Competitividad, Gobierno de España (RTI2018-096068)
- "la Caixa" Foundation (LaCaixa-HR17-00040)
- EC | European Research Council (Advanced Grant-741538)
- Howard Hughes Medical Institute (55007426)
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