Počet záznamů: 1
Wars2 is a determinant of angiogenesis
- 1.0461581 - FGÚ 2017 RIV GB eng J - Článek v odborném periodiku
Wang, 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, Josef - Mráček, Tomáš - Nůsková, Hana - Mikell, B. - Tan, J. - Pesce, F. - Kolář, František - Bottolo, L. - Mancini, M. - Hubner, N. - Pravenec, Michal - Petretto, E. - MacRae, C. - Cook, S. A.
Wars2 is a determinant of angiogenesis.
Nature Communications. Roč. 7, Jul (2016), s. 12061. E-ISSN 2041-1723
Grant CEP: GA MŠk(CZ) LL1204; GA ČR(CZ) GB14-36804G; GA MZd(CZ) NT12370
Institucionální podpora: RVO:67985823
Klíčová slova: Wars2 mutant gene * angiogenesis * coronary flow * spontaneously hypertensive rat
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 12.124, rok: 2016
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.
Trvalý link: http://hdl.handle.net/11104/0261191
Počet záznamů: 1