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Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1
Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signa...
| Autores principales: | , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2017
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603578/ https://www.ncbi.nlm.nih.gov/pubmed/28924218 http://dx.doi.org/10.1038/s41467-017-00654-w |
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| author | Wang, Yidong Wu, Bingruo Lu, Pengfei Zhang, Donghong Wu, Brian Varshney, Shweta del Monte-Nieto, Gonzalo Zhuang, Zhenwu Charafeddine, Rabab Kramer, Adam H. Sibinga, Nicolas E. Frangogiannis, Nikolaos G. Kitsis, Richard N. Adams, Ralf H. Alitalo, Kari Sharp, David J. Harvey, Richard P. Stanley, Pamela Zhou, Bin |
| author_facet | Wang, Yidong Wu, Bingruo Lu, Pengfei Zhang, Donghong Wu, Brian Varshney, Shweta del Monte-Nieto, Gonzalo Zhuang, Zhenwu Charafeddine, Rabab Kramer, Adam H. Sibinga, Nicolas E. Frangogiannis, Nikolaos G. Kitsis, Richard N. Adams, Ralf H. Alitalo, Kari Sharp, David J. Harvey, Richard P. Stanley, Pamela Zhou, Bin |
| author_sort | Wang, Yidong |
| collection | PubMed |
| description | Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure. Simultaneous VEGFR2 inactivation fully rescues these defects. These findings show that dysregulated angiogenic precursors link coronary anomalies to ischemic heart disease. |
| format | Online Article Text |
| id | pubmed-5603578 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-56035782017-09-22 Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1 Wang, Yidong Wu, Bingruo Lu, Pengfei Zhang, Donghong Wu, Brian Varshney, Shweta del Monte-Nieto, Gonzalo Zhuang, Zhenwu Charafeddine, Rabab Kramer, Adam H. Sibinga, Nicolas E. Frangogiannis, Nikolaos G. Kitsis, Richard N. Adams, Ralf H. Alitalo, Kari Sharp, David J. Harvey, Richard P. Stanley, Pamela Zhou, Bin Nat Commun Article Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure. Simultaneous VEGFR2 inactivation fully rescues these defects. These findings show that dysregulated angiogenic precursors link coronary anomalies to ischemic heart disease. Nature Publishing Group UK 2017-09-18 /pmc/articles/PMC5603578/ /pubmed/28924218 http://dx.doi.org/10.1038/s41467-017-00654-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Wang, Yidong Wu, Bingruo Lu, Pengfei Zhang, Donghong Wu, Brian Varshney, Shweta del Monte-Nieto, Gonzalo Zhuang, Zhenwu Charafeddine, Rabab Kramer, Adam H. Sibinga, Nicolas E. Frangogiannis, Nikolaos G. Kitsis, Richard N. Adams, Ralf H. Alitalo, Kari Sharp, David J. Harvey, Richard P. Stanley, Pamela Zhou, Bin Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1 |
| title | Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1 |
| title_full | Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1 |
| title_fullStr | Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1 |
| title_full_unstemmed | Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1 |
| title_short | Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1 |
| title_sort | uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking pofut1 |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603578/ https://www.ncbi.nlm.nih.gov/pubmed/28924218 http://dx.doi.org/10.1038/s41467-017-00654-w |
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