This paper has been peer reviewed.
Frontiers in Research: Evolving Concepts of the Renin–Angiotensin System
Emerging markers in cardiovascular disease: Where does angiotensin-converting enzyme 2 fit in?
Article first published online: 29 JUL 2013
© 2013 The Authors Clinical and Experimental Pharmacology and Physiology © 2013 Wiley Publishing Asia Pty Ltd
Clinical and Experimental Pharmacology and Physiology
Volume 40, Issue 8, pages 551–559, August 2013
How to Cite
Patel, S. K., Velkoska, E. and Burrell, L. M. (2013), Emerging markers in cardiovascular disease: Where does angiotensin-converting enzyme 2 fit in?. Clinical and Experimental Pharmacology and Physiology, 40: 551–559. doi: 10.1111/1440-1681.12069
- Issue published online: 29 JUL 2013
- Article first published online: 29 JUL 2013
- Accepted manuscript online: 23 FEB 2013 06:57AM EST
- Manuscript Accepted: 19 FEB 2013
- Manuscript Revised: 13 FEB 2013
- Manuscript Received: 6 NOV 2012
- National Health and Medical Research Council of Australia. Grant Number: ID1048285
- angiotensin-converting enzyme 2;
- cardiovas-cular disease;
- coronary artery disease;
- heart failure;
- renin–angiotensin system
- The renin–angiotensin system plays a major role in the pathophysiology of cardiovascular disease (CVD). The enzyme angiotensin-converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor AngII and was thought, until recently, to be the main effector of the system.
- The enzyme ACE2, discovered in 2000, can counterbalance the effects of ACE through degradation of AngII and generation of Ang-(1–7). Angiotensin-converting enzyme 2 is abundantly expressed in the heart and localized to the endothelial cells of coronary vessels and smooth muscle cells. Its catalytically active ectodomain undergoes shedding, resulting in ACE2 in the circulation.
- There are 10 studies to date that have measured circulating ACE2 activity in humans, including in healthy subjects and those with heart failure, Type 1 diabetes, implantable cardioverter/defibrillator, elderly subjects undergoing emergency orthopaedic surgery and kidney transplant patients. The results suggest that circulating ACE2 activity may be a marker of CVD, with low levels in healthy individuals and increased levels in those with cardiovascular risk factors or disease. Whether increased plasma ACE2 activity reflects increased synthesis from tissue ACE2 mRNA or increased shedding of tissue ACE2 remains to be determined.
- Angiotensin-converting enzyme 2 is located on the X-chromosome and circulating ACE2 levels are higher in men than in women.
- Large clinical studies in CVD are needed to more precisely clarify the role of ACE2 as a biomarker of CVD, determine the prognostic significance of circulating ACE2 activity and assess whether the measurement of ACE2 will improve CVD risk prediction.