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Recombinant Human Angiotensin-Converting Enzyme 2 as a New Renin-Angiotensin System Peptidase for Heart Failure Therapy

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Abstract

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes several peptides, including the degradation of angiotensin (Ang) II, a peptide with vasoconstrictive/proliferative effects, to generate Ang 1-7, which exerts vasodilatory/antiproliferative actions by acting through its receptor Mas. ACE2 is a multifunctional enzyme, and its actions on other vasoactive peptides, including the apelin-13 and apelin-17 peptides, also can contribute to its cardiovascular effects. The classical pathway of the renin-angiotensin system involving the ACE-Ang II-Ang II type-1 receptor axis is antagonized by the second arm constituted by the ACE2/Ang 1-7/Mas receptor axis. Loss of ACE2 enhances the adverse pathological remodeling susceptibility to pressure overload and myocardial infarction. Human recombinant ACE2 also is a negative regulator of Ang II–induced myocardial hypertrophy, fibrosis, and diastolic dysfunction and suppresses pressure overload–induced heart failure. Due to its characteristics, the ACE2/Ang 1-7/Mas axis may represent new possibilities for developing novel therapeutic strategies for the treatment of hypertension and heart failure. This review summarizes the beneficial effects of ACE2 in heart disease and the potential use of human recombinant ACE2 as a novel therapy for heart failure.

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Acknowledgements

Dr. Gavin Y. Oudit is a Clinician-Investigator of the Alberta Innovates—Health Solutions and the Distinguish Clinician Scientist of the Heart and Stroke Foundation of Canada and Canadian Institutes of Health Research.

Funding

The authors acknowledge financial support from the Canadian Institutes of Health Research (grant 86602 [Dr. Gavin Y. Oudit]), Alberta Innovates–Health Solutions (Dr. Oudit), and the Austrian Academy of Sciences (Dr. Josef M. Penninger).

Disclosures

Dr. G.Y. Oudit: none. Dr. Josef M. Penninger has received grants from the European Union and is a member of the board of, and holds stock interest in, Apeiron Biologics.

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  1. Department of Physiology, Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada

    Gavin Y. Oudit

  2. Institute of Molecular Biotechnology, Vienna, Austria

    Josef M. Penninger

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Correspondence to Gavin Y. Oudit.

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Oudit, G.Y., Penninger, J.M. Recombinant Human Angiotensin-Converting Enzyme 2 as a New Renin-Angiotensin System Peptidase for Heart Failure Therapy. Curr Heart Fail Rep 8, 176–183 (2011). https://doi.org/10.1007/s11897-011-0063-7

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