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This Article Full Text Full Text (PDF) All Versions of this Article: 93/5/685    most recent expphysiol.2007.040352v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lew, R. A. Articles by Smith, A. I. Search for Related Content PubMed PubMed Citation Articles by Lew, R. A. Articles by Smith, A. I. Related Collections Themed Issue papers Cardiovascular control

¹ Department of Biochemistry & Molecular Biology, Monash University, Clayton, Victoria, Australia ² Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia

Angiotensin-converting enzyme 2 (ACE2) is thought to act in an opposing manner to its homologue, angiotensin-converting enzyme (ACE), by inactivating the vasoconstrictor peptide angiotensin II and generating the vasodilatory fragment, angiotensin(1–7). Both ACE and ACE2 are membrane-bound ectoenzymes and may circulate in plasma as a consequence of a proteolytic shedding event. In this study, we show that ACE2 circulates in human plasma, but its activity is suppressed by the presence of an endogenous inhibitor. Partial purification of this inhibitor indicated that the inhibitor is small, hydrophilic and cationic, but not a divalent metal cation. These observations led us to develop a method for removal of the inhibitor, thus allowing detection of plasma ACE2 levels using a sensitive quenched fluorescent substrate-based assay. Using this technique, ACE2 activity measured in plasma from healthy volunteers (n = 18) ranged from 1.31 to 8.69 pmol substrate cleaved min^–1 ml^–1 (mean ± S.E.M., 4.44 ± 0.56 pmol min^–1 ml^–1). Future studies of patients with cardiovascular, renal and liver disease will determine whether plasma ACE2 is elevated in parallel with increased tissue levels observed in these conditions.

(Received 21 October 2007; accepted after revision 9 January 2008; first published online 25 January 2008)
Corresponding author A. I. Smith: Department of Biochemistry & Molecular Biology, PO Box 13D, Monash University, Clayton, Victoria 3800, Australia. Email: ian.smith{at}med.monash.edu.au