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Nature Research, Nature Communications, 1(7), 2016

DOI: 10.1038/ncomms12061

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Wars2 is a determinant of angiogenesis

Journal article published in 2016 by Mao Wang, Patrick Sips ORCID, Ester Khin, Maxime Rotival, Ximing Sun, Rizwan Ahmed, Anissa Anindya Widjaja, Sebastian Schafer ORCID, Permeen Yusoff, Pervinder Kaur Choksi, Nicole Shi Jie Ko, Manvendra K. Singh, David Epstein, Yuguang Guan, Josef Houstek and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractCoronary 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.