Angiotensin-converting enzyme 2 catalytic activity in human plasma is masked by an endogenous inhibitor

Rebecca Ann Lew, Fiona Jane Warner, Iresha Hanchapola, Michael Anthony Yarski, Jay Manohar, Louise M Burrell, Alexander Ian Smith

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Abstract

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 pmoles substrate cleaved/min/mL (mean +/- S.E.M. = 4.44 +/- 0.56 pmol/min/mL). 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.
Original languageEnglish
Pages (from-to)685 - 693
Number of pages9
JournalExperimental Physiology
Volume93
Issue number5
Publication statusPublished - 2008

Cite this

Lew, R. A., Warner, F. J., Hanchapola, I., Yarski, M. A., Manohar, J., Burrell, L. M., & Smith, A. I. (2008). Angiotensin-converting enzyme 2 catalytic activity in human plasma is masked by an endogenous inhibitor. Experimental Physiology, 93(5), 685 - 693.