%0 Journal Article
%T Angiotensin-converting enzyme 2 autoantibodies: further evidence for a role of the renin-angiotensin system in inflammation
%A Mark C Chappell
%J Arthritis Research & Therapy
%D 2010
%I BioMed Central
%R 10.1186/ar3052
%X The discovery of the angiotensin-converting enzyme (ACE) homolog ACE2 [EC 3.4.15.1] has provoked intensive efforts to elucidate the role of this enzyme in various pathologies, including hypertension, diabetes, heart failure, viral infection, pulmonary injury and liver fibrosis. The biological relevance of ACE2 reflects its critical location in the enzymatic cascade of the renin-angiotensin system to directly govern the local expression of angiotensin (Ang) II and Ang-(1-7), two bioactive hormones with significant and opposing actions.In the present issue of Arthritis Research & Therapy, Takahashi and colleagues assessed circulating levels of ACE2 in patients with connective tissue pathologies including pulmonary hypertension and persistent digital ischemia [1]. In comparison with normal controls, patients with overt vasculopathy expressed significantly higher amounts of ACE2 protein in the circulation. These patients, however, exhibited reduced ACE2 activity in serum and circulating autoantibodies against the enzyme. There are few reports on the circulating levels of ACE2 in humans or experimental models, possibly reflecting the difficulty of obtaining a consistent measurement of the enzymatic activity. The current study reveals a potentially novel mechanism to attenuate the catalytic activity of ACE2, thereby promoting the inflammatory actions of Ang II.ACE and ACE2 are both chloride-activated metallopeptidases that are predominantly associated with the cell membrane and are widely distributed in various tissues and vascular beds. In contrast to ACE, which cleaves two amino acid residues from the carboxyl terminus of Ang I to form Ang II, ACE2 hydrolyzes a single amino acid from the carboxyl end of Ang II to form Ang-(1-7) [2]. ACE is considered the primary enzymatic pathway that catalyzes the generation of Ang II in the circulation and tissues. ACE inhibitors, which have become standard therapies in the treatment of hypertension and other cardiovascular disease, h
%U http://arthritis-research.com/content/12/3/128