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Angiotensin-converting enzyme 2 is an essential regulator of heart function

Author

Listed:
  • Michael A. Crackower

    (Amgen Research Institute/Ontario Cancer Institute, University of Toronto
    University of Toronto
    The Heart & Stroke/Richard Lewar Centre for Excellence in Cardiovascular Research, University of Toronto)

  • Renu Sarao

    (Amgen Research Institute/Ontario Cancer Institute, University of Toronto
    IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences)

  • Gavin Y. Oudit

    (The Heart & Stroke/Richard Lewar Centre for Excellence in Cardiovascular Research, University of Toronto
    University of Toronto
    University of Toronto)

  • Chana Yagil

    (Faculty of Health Science, Ben-Gurion University Barzilai Medical Center Campus)

  • Ivona Kozieradzki

    (Amgen Research Institute/Ontario Cancer Institute, University of Toronto
    IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences)

  • Sam E. Scanga

    (University Health Network, Ontario Cancer Institute, University of Toronto)

  • Antonio J. Oliveira-dos-Santos

    (Amgen Research Institute/Ontario Cancer Institute, University of Toronto)

  • Joan da Costa

    (Amgen Research Institute/Ontario Cancer Institute, University of Toronto)

  • Liyong Zhang

    (Amgen Research Institute/Ontario Cancer Institute, University of Toronto
    University of Toronto
    The Heart & Stroke/Richard Lewar Centre for Excellence in Cardiovascular Research, University of Toronto
    IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences)

  • York Pei

    (University of Toronto)

  • James Scholey

    (University of Toronto)

  • Carlos M. Ferrario

    (The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine)

  • Armen S. Manoukian

    (University Health Network, Ontario Cancer Institute, University of Toronto)

  • Mark C. Chappell

    (The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine)

  • Peter H. Backx

    (The Heart & Stroke/Richard Lewar Centre for Excellence in Cardiovascular Research, University of Toronto
    University of Toronto
    University of Toronto)

  • Yoram Yagil

    (University of Toronto)

  • Josef M. Penninger

    (Amgen Research Institute/Ontario Cancer Institute, University of Toronto
    University of Toronto
    The Heart & Stroke/Richard Lewar Centre for Excellence in Cardiovascular Research, University of Toronto
    IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences)

Abstract

Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. Here we show that angiotensin-converting enzyme 2 (ace2) maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension. In all hypertensive rat strains, ACE2 messenger RNA and protein expression were markedly reduced, suggesting that ace2 is a candidate gene for this QTL. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart. Genetic ablation of ACE on an ACE2 mutant background completely rescues the cardiac phenotype. But disruption of ACER, a Drosophila ACE2 homologue, results in a severe defect of heart morphogenesis. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo.

Suggested Citation

  • Michael A. Crackower & Renu Sarao & Gavin Y. Oudit & Chana Yagil & Ivona Kozieradzki & Sam E. Scanga & Antonio J. Oliveira-dos-Santos & Joan da Costa & Liyong Zhang & York Pei & James Scholey & Carlos, 2002. "Angiotensin-converting enzyme 2 is an essential regulator of heart function," Nature, Nature, vol. 417(6891), pages 822-828, June.
    • Handle: RePEc:nat:nature:v:417:y:2002:i:6891:d:10.1038_nature00786
    DOI: 10.1038/nature00786
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    Cited by:

    1. Tomokazu Yamaguchi & Midori Hoshizaki & Takafumi Minato & Satoru Nirasawa & Masamitsu N. Asaka & Mayumi Niiyama & Masaki Imai & Akihiko Uda & Jasper Fuk-Woo Chan & Saori Takahashi & Jianbo An & Akari , 2021. "ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Milad Haghani & Pegah Varamini, 2021. "Temporal evolution, most influential studies and sleeping beauties of the coronavirus literature," Scientometrics, Springer;Akadémiai Kiadó, vol. 126(8), pages 7005-7050, August.
    3. Joshua M Akey & Michael A Eberle & Mark J Rieder & Christopher S Carlson & Mark D Shriver & Deborah A Nickerson & Leonid Kruglyak, 2004. "Population History and Natural Selection Shape Patterns of Genetic Variation in 132 Genes," PLOS Biology, Public Library of Science, vol. 2(10), pages 1-1, September.

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