Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms12061
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dc.titleWars2 is a determinant of angiogenesis
dc.contributor.authorWang M.
dc.contributor.authorSips P.
dc.contributor.authorKhin E.
dc.contributor.authorRotival M.
dc.contributor.authorSun X.
dc.contributor.authorAhmed R.
dc.contributor.authorWidjaja A.A.
dc.contributor.authorSchafer S.
dc.contributor.authorYusoff P.
dc.contributor.authorChoksi P.K.
dc.contributor.authorKo N.S.J.
dc.contributor.authorSingh M.K.
dc.contributor.authorEpstein D.
dc.contributor.authorGuan Y.
dc.contributor.authorHouštěk J.
dc.contributor.authorMracek T.
dc.contributor.authorNuskova H.
dc.contributor.authorMikell B.
dc.contributor.authorTan J.
dc.contributor.authorPesce F.
dc.contributor.authorKolar F.
dc.contributor.authorBottolo L.
dc.contributor.authorMancini M.
dc.contributor.authorHubner N.
dc.contributor.authorPravenec M.
dc.contributor.authorPetretto E.
dc.contributor.authorMacrae C.
dc.contributor.authorCook S.A.
dc.date.accessioned2019-01-15T08:19:08Z
dc.date.available2019-01-15T08:19:08Z
dc.date.issued2016-07-08
dc.identifier.citationWang M., Sips P., Khin E., Rotival M., Sun X., Ahmed R., Widjaja A.A., Schafer S., Yusoff P., Choksi P.K., Ko N.S.J., Singh M.K., Epstein D., Guan Y., Houštěk J., Mracek T., Nuskova H., Mikell B., Tan J., Pesce F., Kolar F., Bottolo L., Mancini M., Hubner N., Pravenec M., Petretto E., Macrae C., Cook S.A. (2016-07-08). Wars2 is a determinant of angiogenesis. Nature Communications 7. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms12061
dc.identifier.issn20411723
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/150844
dc.description.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.
dc.publisherNature Publishing Group
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1038/ncomms12061
dc.description.sourcetitleNature Communications
dc.description.volume7
dc.published.statePublished
dc.grant.idMC_U120097112
dc.grant.idG1002319
dc.grant.fundingagencyMRC, Medical Research Council
dc.grant.fundingagencyMRC, Medical Research Council
dc.description.redepositCompleted
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