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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Nat+Commun
2016 ; 7
(ä): 12061
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Wars2 is a determinant of angiogenesis
#MMPMID27389904
Wang M
; Sips P
; Khin E
; Rotival M
; Sun X
; Ahmed R
; Widjaja AA
; Schafer S
; Yusoff P
; Choksi PK
; Ko NS
; Singh MK
; Epstein D
; Guan Y
; Hou?t?k 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 SA
Nat Commun
2016[Jul]; 7
(ä): 12061
PMID27389904
show ga
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.
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