Wars2 is a determinant of angiogenesis.
Nat Commun
; 7: 12061, 2016 07 08.
Article
in En
| MEDLINE
| ID: mdl-27389904
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.
Full text:
1
Database:
MEDLINE
Main subject:
Tryptophan-tRNA Ligase
/
Genome
/
Gene Expression Regulation, Developmental
/
Neovascularization, Physiologic
/
Human Umbilical Vein Endothelial Cells
/
Mitochondria
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2016
Type:
Article
Affiliation country:
Singapore