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Wars2 is a determinant of angiogenesis

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Item Type:Article
Title:Wars2 is a determinant of angiogenesis
Creators Name:Wang, M. and Sips, P. and Khin, E. and Rotival, M. and Sun, X. and Ahmed, R. and Widjaja, A.A. and Schafer, S. and Yusoff, P. and Choksi, Pe.K. and Ko, N.S.J. and Singh, M.K. and Epstein, D. and Guan, Y. and Houstek, J. and Mracek, T. and Nuskova, H. and Mikell, B. and Tan, J. and Pesce, F. and Kolar, F. and Bottolo, L. and Mancini, M. and Hubner, N. and Pravenec, M. and Petretto, E. and MacRae, C. and Cook, S.A.
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.
Keywords:Animals, Rats
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:7
Page Range:12061
Date:8 July 2016
Official Publication:https://doi.org/10.1038/ncomms12061
PubMed:View item in PubMed

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