Received October 31, 2007
Revised December 7, 2007
Accepted after revision January 22, 2008
Heart/Cardiac Muscle [240]
|
Functional angiotensin converting enzyme-2 (ACE2) is expressed in human cardiac myofibroblasts
Jodie L Guy 1,
Daniel W Lambert 1,
Anthony J Turner 2*,
Karen E Porter 1
1 University of Leeds
2 Leeds University
* To whom correspondence should be addressed. E-mail: a.j.turner{at}leeds.ac.uk.
 |
Abstract |
|---|
The renin-angiotensin system (RAS), in particular angiotensin II, plays an important role in cardiac remodelling. ACE and ACE2 are key players in the RAS and act antagonistically to regulate the levels of angiotensin II. In this study we reveal the functional expression of ACE2 in human cardiac myofibroblasts, cells that are essential to the maintenance of normal cardiac architecture and also play a key role in myocardial remodelling. The observed reciprocal expression of ACE and ACE2 in these cells may reflect the possible opposing activity of these two enzymes.
In this study we demonstrated the presence of ACE2 as an ectoenzyme and revealed that ACE2 undergoes PMA-inducible ectodomain shedding from the membrane. When cells were exposed to a number of pathophysiological stimuli, modulation of ACE2 levels was not detected. Importantly, whilst we found ACE2 to be expressed constitutively in cardiac myofibroblasts there were no detectable levels in either vascular smooth muscle cells or vascular endothelium, indicating that ACE2 expression is not ubiquitous. In paraffin sections of atrial appendage tissue we observed a distinct staining pattern for ACE2 which appeared different from that of ACE.
In conclusion, this study is the first to report co-expression of ACE and ACE2 in human cardiac myofibroblasts and may therefore present a model primary system to study the comparative cell biology of ACE2 and ACE and their potentially opposing roles in myocardial remodelling.
Key Words:
Angiotensin, Enzyme, Fibroblast
