Wars2 is a determinant of angiogenesis

被引：47

作者：

Wang, Mao ^{[1
,2
]}

Sips, Patrick ^{[3
,4
]}

Khin, Ester ^{[1
]}

Rotival, Maxime ^{[5
]}

Sun, Ximing ^{[5
]}

Ahmed, Rizwan ^{[5
]}

Widjaja, Anissa Anindya ^{[1
]}

Schafer, Sebastian ^{[1
,6
]}

Yusoff, Permeen ^{[1
]}

Choksi, Pervinder Kaur ^{[1
]}

Ko, Nicole Shi Jie ^{[1
]}

Singh, Manvendra K. ^{[1
,6
]}

Epstein, David ^{[1
]}

Guan, Yuguang ^{[1
]}

Houstek, Josef ^{[7
]}

Mracek, Tomas ^{[7
]}

Nuskova, Hana ^{[7
]}

Mikell, Brittney ^{[3
,4
]}

Tan, Jessie ^{[6
]}

Pesce, Francesco ^{[8
]}

Kolar, Frantisek ^{[7
]}

Bottolo, Leonardo ^{[9
]}

Mancini, Massimiliano ^{[10
]}

Hubner, Norbert ^{[11
,12
,13
]}

Pravenec, Michal ^{[7
]}

Petretto, Enrico ^{[1
]}

MacRae, Calum ^{[3
,4
]}

Cook, Stuart A. ^{[1
,6
,8
]}

机构：

[1] Natl Univ Singapore, Duke NUS Med Sch, Cardiovasc & Metab Disorders Program, 8 Coll Rd, Singapore 169857, Singapore

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, 1E Kent Ridge Rd, Singapore 119228, Singapore

[3] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA

[4] Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA

[5] Imperial Coll London, Hammersmith Hosp, MRC, Ctr Clin Sci,Fac Med, Du Cane Rd, London W12 ONN, England

[6] Natl Heart Ctr Singapore, 5 Hosp Dr, Singapore 169609, Singapore

[7] Czech Acad Sci, Inst Physiol, Prague 14220 4, Czech Republic

[8] Imperial Coll London, Natl Heart & Lung Inst, Royal Brompton Campus, London SW3 6NP, England

[9] Imperial Coll London, Dept Math, South Kensington Campus, London SW7 2AZ, England

[10] Univ Rome, Dept Radiol Oncol & Anatomo Pathol Sci, I-00161 Sapienza, Italy

[11] Max Delbruck Ctr Mol Med MDC, Cardiovasc & Metab Sci, D-13125 Berlin, Germany

[12] Charite, D-10117 Berlin, Germany

[13] Partner Site Berlin, DZHK German Ctr Cardiovasc Res, D-13125 Berlin, Germany

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

关键词：

TRANSFER-RNA-SYNTHETASE; CORONARY VASCULATURE; CARDIAC-HYPERTROPHY; ZEBRAFISH; BLOOD; HEART; DEFICIENCY; REVEALS; CONTRIBUTES; MECHANISMS;

D O I：

10.1038/ncomms12061

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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