Wars2 is a determinant of angiogenesis
View/ Open
Author
Wang, Mao
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
Cook, Stuart A
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/ncomms12061Metadata
Show full item recordCitation
Wang, M., P. Sips, E. Khin, M. Rotival, X. Sun, R. Ahmed, A. A. Widjaja, et al. 2016. “Wars2 is a determinant of angiogenesis.” Nature Communications 7 (1): 12061. doi:10.1038/ncomms12061. http://dx.doi.org/10.1038/ncomms12061.Abstract
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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941120/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407658
Collections
- HMS Scholarly Articles [17917]
Contact administrator regarding this item (to report mistakes or request changes)