%0 Journal Article
%T Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease
%A Chris Tikellis
%A M. C. Thomas
%J International Journal of Peptides
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/256294
%X Angiotensin-converting enzyme 2 (ACE2) shares some homology with angiotensin-converting enzyme (ACE) but is not inhibited by ACE inhibitors. The main role of ACE2 is the degradation of Ang II resulting in the formation of angiotensin 1每7 (Ang 1每7) which opposes the actions of Ang II. Increased Ang II levels are thought to upregulate ACE2 activity, and in ACE2 deficient mice Ang II levels are approximately double that of wild-type mice, whilst Ang 1每7 levels are almost undetectable. Thus, ACE2 plays a crucial role in the RAS because it opposes the actions of Ang II. Consequently, it has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease where its expression is decreased. Not surprisingly, current therapeutic strategies for ACE2 involve augmenting its expression using ACE2 adenoviruses, recombinant ACE2 or compounds in these diseases thereby affording some organ protection. 1. Introduction The renin-angiotensin system (RAS) is a signalling pathway that acts as a homeostatic regulator of vascular function [1]. Its systemic actions include the regulation of blood pressure, natriuresis, and blood volume control. However, the RAS also plays an important local role, regulating regional blood flow and controlling trophic responses to a range of stimuli. The RAS is composed of a number of different regulatory components and effector peptides that facilitate the dynamic control of vascular function, in both health and disease (Figure 1). Many of these components have opposing functions to accommodate a rapid but coordinated response to specific triggers. For example, angiotensin I (Ang I) is metabolised by the dipeptide carboxypeptidase, angiotensin-converting enzyme (ACE) to form angiotensin II (Ang II) and Ang II is metabolised by the carboxypeptidase, ACE2, producing the vasodilator, angiotensin(1每7) (Ang 1每7) [2每4]. Historically, ACE and Ang II have been the key focus for clinical interventions targeting the RAS and its pathogenic actions. However, recent studies have also demonstrated the importance of ACE2 in maintaining the balance of the RAS. Indeed, in some settings, and the cardiovascular system in particular, ACE2 may be more important than ACE in regulating local levels of Ang II and Ang 1每7, and therein the balance of RAS activation. For example, we have shown that acquired or genetic deficiency of ACE2 results in increased tissue and circulating levels of Ang II [5, 6] and reduced levels of Ang 1每7 [6]. By contrast, Ace KO mice have modestly reduced circulating Ang II, while tissue levels are not
%U http://www.hindawi.com/journals/ijpep/2012/256294/