Angiotensin-Converting Enzyme 2 Metabolizes and Partially Inactivates Pyr-Apelin-13 and Apelin-17: Physiological Effects in the Cardiovascular System

Wang WangGavin Y Oudit


Apelin peptides mediate beneficial effects on the cardiovascular system and are being targeted as potential new drugs. However, apelin peptides have extremely short biological half-lives, and improved understanding of apelin peptide metabolism may lead to the discovery of biologically stable analogues with therapeutic potential. We examined the ability of angiotensin-converting enzyme 2 (ACE2) to cleave and inactivate pyr-apelin 13 and apelin 17, the dominant apelin peptides. Computer-assisted modeling shows a conserved binding of pyr-apelin 13 and apelin 17 to the ACE2 catalytic site. In ACE2 knockout mice, hypotensive action of pyr-apelin 13 and apelin 17 was potentiated, with a corresponding greater elevation in plasma apelin levels. Similarly, pharmacological inhibition of ACE2 potentiated the vasodepressor action of apelin peptides. Biochemical analysis confirmed that recombinant human ACE2 can cleave pyr-apelin 13 and apelin 17 efficiently, and apelin peptides are degraded slower in ACE2-deficient plasma. The biological relevance of ACE2-mediated proteolytic processing of apelin peptides was further supported by the reduced potency of pyr-apelin 12 and apelin 16 on the activation of signaling pathways and nitric oxide pro...Continue Reading


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Jun 21, 2002·Nature·Michael A CrackowerJosef M Penninger
Oct 3, 2002·Journal of the American Chemical Society·Natalie A DalesMichael A Patane
Feb 3, 2004·The Journal of Biological Chemistry·Paul TowlerMichael W Pantoliano
Jul 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nadia De MotaCatherine Llorens-Cortes
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Aug 9, 2011·The Journal of Clinical Investigation·Tero-Pekka AlastaloMarlene Rabinovitch
Sep 23, 2011·American Journal of Physiology. Renal Physiology·Qiu-Xia ZhangAllan G Murray
Jul 20, 2012·Nature·Maria Cecilia ScimiaPilar Ruiz-Lozano
Nov 2, 2013·The Journal of Clinical Investigation·Teruki SatoKeiji Kuba
Dec 18, 2013·Journal of Molecular and Cellular Cardiology·Vaibhav B PatelGavin Y Oudit
Apr 15, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wang WangGavin Y Oudit
Jul 12, 2014·The Journal of Biological Chemistry·Emilie CeraudoCatherine Llorens-Cortes
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