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Wars2 is a determinant of angiogenesis

Author

Listed:
  • Mao Wang

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Patrick Sips

    (Brigham and Women's Hospital and Harvard Medical School)

  • Ester Khin

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore)

  • Maxime Rotival

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital)

  • Ximing Sun

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital)

  • Rizwan Ahmed

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital)

  • Anissa Anindya Widjaja

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore)

  • Sebastian Schafer

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore
    National Heart Centre Singapore)

  • Permeen Yusoff

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore)

  • Pervinder Kaur Choksi

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore)

  • Nicole Shi Jie Ko

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore)

  • Manvendra K. Singh

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore
    National Heart Centre Singapore)

  • David Epstein

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore)

  • Yuguang Guan

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore)

  • Josef Houštěk

    (Institute of Physiology, Czech Academy of Sciences.)

  • Tomas Mracek

    (Institute of Physiology, Czech Academy of Sciences.)

  • Hana Nuskova

    (Institute of Physiology, Czech Academy of Sciences.)

  • Brittney Mikell

    (Brigham and Women's Hospital and Harvard Medical School)

  • Jessie Tan

    (National Heart Centre Singapore)

  • Francesco Pesce

    (National Heart and Lung Institute, Royal Brompton Campus, Imperial College London)

  • Frantisek Kolar

    (Institute of Physiology, Czech Academy of Sciences.)

  • Leonardo Bottolo

    (South Kensington Campus, Imperial College London)

  • Massimiliano Mancini

    (Oncological and Anatomo-Pathological Sciences, University of Rome)

  • Norbert Hubner

    (Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine (MDC)
    Charité-Universitätsmedizin
    DZHK (German Center for Cardiovascular Research), Partner Site Berlin)

  • Michal Pravenec

    (Institute of Physiology, Czech Academy of Sciences.)

  • Enrico Petretto

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore)

  • Calum MacRae

    (Brigham and Women's Hospital and Harvard Medical School)

  • Stuart A Cook

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, National University of Singapore
    National Heart Centre Singapore
    National Heart and Lung Institute, Royal Brompton Campus, Imperial College London)

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.

Suggested Citation

  • Mao Wang & Patrick Sips & Ester Khin & Maxime Rotival & Ximing Sun & Rizwan Ahmed & Anissa Anindya Widjaja & Sebastian Schafer & Permeen Yusoff & Pervinder Kaur Choksi & Nicole Shi Jie Ko & Manvendra , 2016. "Wars2 is a determinant of angiogenesis," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12061
    DOI: 10.1038/ncomms12061
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    Cited by:

    1. Keith Siew & Kevin A. Nestler & Charlotte Nelson & Viola D’Ambrosio & Chutong Zhong & Zhongwang Li & Alessandra Grillo & Elizabeth R. Wan & Vaksha Patel & Eliah Overbey & JangKeun Kim & Sanghee Yun & , 2024. "Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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