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Wars2 is a determinant of angiogenesis

M. Wang, P. Sips, E. Khin, M. Rotival, X. Sun, R. Ahmed, AA. Widjaja, S. Schafer, P. Yusoff, PK. Choksi, NS. Ko, MK. Singh, D. Epstein, Y. Guan, J. Houštěk, T. Mracek, H. Nuskova, B. Mikell, J. Tan, F. Pesce, F. Kolar, L. Bottolo, M. Mancini, N....

. 2016 ; 7 (-) : 12061. [pub] 20160708

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc18034113

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.

Cardiovascular and Metabolic Disorders Program Duke NUS Medical School National University of Singapore 8 College Road Singapore 169857 Singapore

Cardiovascular and Metabolic Disorders Program Duke NUS Medical School National University of Singapore 8 College Road Singapore 169857 Singapore Department of Medicine Yong Loo Lin School of Medicine National University of Singapore 1E Kent Ridge Road Singapore 119228 Singapore

Cardiovascular and Metabolic Disorders Program Duke NUS Medical School National University of Singapore 8 College Road Singapore 169857 Singapore National Heart Centre Singapore 5 Hospital Drive Singapore 169609 Singapore

Cardiovascular and Metabolic Disorders Program Duke NUS Medical School National University of Singapore 8 College Road Singapore 169857 Singapore National Heart Centre Singapore 5 Hospital Drive Singapore 169609 Singapore National Heart and Lung Institute Royal Brompton Campus Imperial College London London SW3 6NP UK

Cardiovascular and Metabolic Sciences Max Delbrück Center for Molecular Medicine Partner Site Berlin 13125 Berlin Germany

Cardiovascular Division Department of Medicine Brigham and Women's Hospital and Harvard Medical School 75 Francis Street Boston Massachusetts 02115 USA

Department of mathematics South Kensington Campus Imperial College London London SW7 2AZ UK

Department of Radiological Oncological and Anatomo Pathological Sciences University of Rome 00161 Sapienza Italy

Institute of Physiology Czech Academy of Sciences 142 20 Prague 4 Czech Republic

Medical Research Council Clinical Sciences Centre Faculty of Medicine Imperial College London Hammersmith Hospital Du Cane Road London W12 ONN UK

National Heart and Lung Institute Royal Brompton Campus Imperial College London London SW3 6NP UK

National Heart Centre Singapore 5 Hospital Drive Singapore 169609 Singapore

Citace poskytuje Crossref.org

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