Physiological Relevance of Hydrolysis of Atrial Natriuretic Peptide by Endothelin-Converting Enzyme-1

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Author(s)

    • Nakayama Kazuhiko
    • Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
    • Emoto Noriaki
    • Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
    • Suzuki Yoko
    • Department of Clinical Pharmacy, Kobe Pharmaceutical University
    • Yagi Keiko
    • Department of Clinical Pharmacy, Kobe Pharmaceutical University
    • Hirata Ken-Ichi
    • Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine

Abstract

Endothelin-converting enzyme-1 (ECE-1) is a membrane-bound metalloprotease that cleaves biologically inactive big endothelin-1 (ET-1) into active ET-1. ET-1 is involved in the cardiovascular homeostasis and the development of cardiovascular diseases including pulmonary arterial hypertension and heart failure. Atrial natriuretic peptide (ANP) is an endogenous hormone that is released from the heart in response to myocardial stretch and overload. ANP was shown to be hydrolyzed by neutral endopeptidase 24.11 (NEP) which shares important structural features with ECE-1. Previous in vitro studies using recombinant soluble ECE-1 suggested that ECE-1 cleaved several biologically active peptides including ANP in addition to big ET-1. However, physiological relevance of ANP-degrading activity by ECE-1 has stayed unclear. Here, we aimed to investigate whether endogenous ECE-1 is able to hydrolyze ANP using live-cell based assay and ECE-1-deficient mice. Chinese hamster ovary (CHO) cells, which lack detectable levels of ECE activity, degraded ANP in the medium efficiently when transfected with ECE-1 cDNA. ANP peptide contents in the E14-15 embryos were significantly higher in ECE-1+/- mice compared with ECE-1+/+ mice. These observations strongly suggest that ECE-1 is involved in the physiological degradation of ANP in vivo. Thus, pharmacological inhibition of ECE-1 may provide a novel strategy to treat various cardiovascular diseases by suppressing and potentiating the ET and ANP pathway, respectively.

Journal

  • The Kobe journal of the medical sciences

    The Kobe journal of the medical sciences 58(1), 12-18, 2012

    Kobe University

Codes

  • NII Article ID (NAID)
    110009591545
  • NII NACSIS-CAT ID (NCID)
    AA00711740
  • Text Lang
    ENG
  • Article Type
    departmental bulletin paper
  • ISSN
    0023-2513
  • Data Source
    NII-ELS  IR 
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