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Wars2 is a determinant of angiogenesis
Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart in vivo. Here we exploit this relationship and show that CF in the rat is influenced by a locus on rat chromosome 2 that is also associated with cardiac capillary den...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941120/ https://www.ncbi.nlm.nih.gov/pubmed/27389904 http://dx.doi.org/10.1038/ncomms12061 |
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author | Wang, Mao Sips, Patrick Khin, Ester Rotival, Maxime Sun, Ximing Ahmed, Rizwan Widjaja, Anissa Anindya Schafer, Sebastian Yusoff, Permeen Choksi, Pervinder Kaur Ko, Nicole Shi Jie Singh, Manvendra K. Epstein, David Guan, Yuguang Houštěk, Josef Mracek, Tomas Nuskova, Hana Mikell, Brittney Tan, Jessie Pesce, Francesco Kolar, Frantisek Bottolo, Leonardo Mancini, Massimiliano Hubner, Norbert Pravenec, Michal Petretto, Enrico MacRae, Calum Cook, Stuart A |
author_facet | Wang, Mao Sips, Patrick Khin, Ester Rotival, Maxime Sun, Ximing Ahmed, Rizwan Widjaja, Anissa Anindya Schafer, Sebastian Yusoff, Permeen Choksi, Pervinder Kaur Ko, Nicole Shi Jie Singh, Manvendra K. Epstein, David Guan, Yuguang Houštěk, Josef Mracek, Tomas Nuskova, Hana Mikell, Brittney Tan, Jessie Pesce, Francesco Kolar, Frantisek Bottolo, Leonardo Mancini, Massimiliano Hubner, Norbert Pravenec, Michal Petretto, Enrico MacRae, Calum Cook, Stuart A |
author_sort | Wang, Mao |
collection | PubMed |
description | Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart in vivo. Here we exploit this relationship and show that CF in the rat is influenced by a locus on rat chromosome 2 that is also associated with cardiac capillary density. Mitochondrial tryptophanyl-tRNA synthetase (Wars2), encoding an L53F protein variant within the ATP-binding motif, is prioritized as the candidate at the locus by integrating genomic data sets. WARS2(L53F) has low enzyme activity and inhibition of WARS2 in endothelial cells reduces angiogenesis. In the zebrafish, inhibition of wars2 results in trunk vessel deficiencies, disordered endocardial-myocardial contact and impaired heart function. Inhibition of Wars2 in the rat causes cardiac angiogenesis defects and diminished cardiac capillary density. Our data demonstrate a pro-angiogenic function for Wars2 both within and outside the heart that may have translational relevance given the association of WARS2 with common human diseases. |
format | Online Article Text |
id | pubmed-4941120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49411202016-09-06 Wars2 is a determinant of angiogenesis Wang, Mao Sips, Patrick Khin, Ester Rotival, Maxime Sun, Ximing Ahmed, Rizwan Widjaja, Anissa Anindya Schafer, Sebastian Yusoff, Permeen Choksi, Pervinder Kaur Ko, Nicole Shi Jie Singh, Manvendra K. Epstein, David Guan, Yuguang Houštěk, Josef Mracek, Tomas Nuskova, Hana Mikell, Brittney Tan, Jessie Pesce, Francesco Kolar, Frantisek Bottolo, Leonardo Mancini, Massimiliano Hubner, Norbert Pravenec, Michal Petretto, Enrico MacRae, Calum Cook, Stuart A Nat Commun Article Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart in vivo. Here we exploit this relationship and show that CF in the rat is influenced by a locus on rat chromosome 2 that is also associated with cardiac capillary density. Mitochondrial tryptophanyl-tRNA synthetase (Wars2), encoding an L53F protein variant within the ATP-binding motif, is prioritized as the candidate at the locus by integrating genomic data sets. WARS2(L53F) has low enzyme activity and inhibition of WARS2 in endothelial cells reduces angiogenesis. In the zebrafish, inhibition of wars2 results in trunk vessel deficiencies, disordered endocardial-myocardial contact and impaired heart function. Inhibition of Wars2 in the rat causes cardiac angiogenesis defects and diminished cardiac capillary density. Our data demonstrate a pro-angiogenic function for Wars2 both within and outside the heart that may have translational relevance given the association of WARS2 with common human diseases. Nature Publishing Group 2016-07-08 /pmc/articles/PMC4941120/ /pubmed/27389904 http://dx.doi.org/10.1038/ncomms12061 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wang, Mao Sips, Patrick Khin, Ester Rotival, Maxime Sun, Ximing Ahmed, Rizwan Widjaja, Anissa Anindya Schafer, Sebastian Yusoff, Permeen Choksi, Pervinder Kaur Ko, Nicole Shi Jie Singh, Manvendra K. Epstein, David Guan, Yuguang Houštěk, Josef Mracek, Tomas Nuskova, Hana Mikell, Brittney Tan, Jessie Pesce, Francesco Kolar, Frantisek Bottolo, Leonardo Mancini, Massimiliano Hubner, Norbert Pravenec, Michal Petretto, Enrico MacRae, Calum Cook, Stuart A Wars2 is a determinant of angiogenesis |
title | Wars2 is a determinant of angiogenesis |
title_full | Wars2 is a determinant of angiogenesis |
title_fullStr | Wars2 is a determinant of angiogenesis |
title_full_unstemmed | Wars2 is a determinant of angiogenesis |
title_short | Wars2 is a determinant of angiogenesis |
title_sort | wars2 is a determinant of angiogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941120/ https://www.ncbi.nlm.nih.gov/pubmed/27389904 http://dx.doi.org/10.1038/ncomms12061 |
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