Cloning and characterization of a secreted form of angiotensin-converting enzyme 2

Regulatory Peptides
Matthew J HuentelmanM K Raizada

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a newly discovered, membrane-bound aminopeptidase responsible for the production of vasodilatory peptides such as angiotensin 1-7 (Ang 1-7). Thus, ACE2 is important in counteracting the adverse, vasoconstrictor effects of angiotensin II (Ang II). The objective of the present study was to clone and characterize a constitutively secreted form of ACE2 as a prelude to an investigation into its therapeutic potential in hypertension. A truncated form of ACE2 was cloned into a lentiviral vector behind the human elongation factor 1 alpha promoter (lenti-shACE2). Transfection experiments demonstrated that secreted human ACE2 (shACE2) was secreted constitutively into the medium. The kinetic properties of shACE2 were comparable to the human recombinant enzyme (rACE2). Transduction of human coronary artery endothelial cells and rat cardiomyocytes with lenti-shACE2 showed a significant secretion of the enzyme into the medium compared to its native, membrane-bound homolog (human ACE2 [hACE2]). In addition, systemic administration of lenti-shACE2 into neonatal rats resulted in a eightfold increase in ACE2 activity in the serum above control values. These observations establish that lenti-shACE2 can be...Continue Reading

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Citations

Mar 1, 2008·Future Cardiology·Anderson J FerreiraMohan K Raizada
Jan 30, 2010·Molecular Medicine·Rodrigo A Fraga-SilvaAnderson J Ferreira
Jul 2, 2011·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Masanobu YamazatoMohan K Raizada
Sep 2, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Kim Brint PedersenEric Lazartigues
Sep 29, 2011·Cardiovascular Research·Srinivas SriramulaJoseph Francis
Jul 28, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Amrisha VermaQiuhong Li
Jul 13, 2005·Progress in Biophysics and Molecular Biology·Shant Der SarkissianMohan K Raizada
Apr 1, 2014·Clinical and Experimental Hypertension : CHE·Yongdong LiDan Liu
Jan 11, 2005·Experimental Physiology·Michael J KatovichMohan K Raizada
Apr 6, 2006·Hypertension·Khalid M ElasedMariana Morris
Dec 14, 2005·Hypertension·Mohan K Raizada, Shant Der Sarkissian
Oct 20, 2004·Hypertension·Matthew J HuentelmanDavid A Ostrov
Jun 22, 2006·Physiological Genomics·Carlos Díez-FreireMohan K Raizada
Jul 15, 2015·American Journal of Physiology. Heart and Circulatory Physiology·Liping ZhuXiao-Ping Yang
Sep 18, 2009·American Journal of Physiology. Cell Physiology·Michikado IwataBarry H Greenberg
Jun 30, 2007·Clinical Science·Justin L GrobeMichael J Katovich
Feb 20, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Aaron J TraskCarlos M Ferrario
Apr 19, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Michiya IgaseCarlos M Ferrario
Sep 10, 2020·Frontiers in Microbiology·Igor de Andrade SantosAna Carolina Gomes Jardim
Jul 8, 2020·Cells·Nazzarena LabòGiovanna Tosato
May 11, 2021·Frontiers in Neuroscience·Lucas M KangussuMaria José Campagnole-Santos

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