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(Circulation Research. 2008;103:1197.)
© 2008 American Heart Association, Inc.

Editorials

The Angiotensin Converting Enzyme 2/Ang-(1-7) Axis in the Heart

A Role for Mas Communication?

James A. Stewart, Jr, Eric Lazartigues, Pamela A. Lucchesi

From the Center for Cardiovascular and Pulmonary Research (J.A.S., P.A.L.), Research Institute & The Heart Center, Nationwide Children’s Hospital, Columbus, Ohio; and Department of Pharmacology and Experimental Therapeutics (E.L.), Louisiana State University Health Science Center, New Orleans.

Correspondence to Pamela A. Lucchesi, PhD, Center for Cardiovascular and Pulmonary Research Nationwide Children’s Hospital, 700 Children’s Dr, W303, Columbus, OH 43205. E-mail pamela.lucchesi@nationwidechildrens.org

An extract of the first 250 words of the full text is provided, because this article has no abstract.

For decades, the literature has been inundated with evidence of the important role of the renin–angiotensin system (RAS) in cardiac remodeling and function with most in the field familiar with this classic, dogmatic story. The protease renin is synthesized and released from the kidney and acts on a circulating inactive peptide, angiotensinogen, produced by the liver, giving rise to angiotensin (Ang) I. Ang I is then transformed into the biologically active octapeptide, Ang II, through enzymatic cleavage by angiotensin-converting enzyme (ACE).¹ Ang II is the main effector molecule of the RAS, acting in an endocrine, autocrine/paracrine, and intracrine hormone pathway on cardiac cells. Ang II binds and activates G protein–coupled receptors, the angiotensin type 1 (AT₁R) and angiotensin type 2 (AT₂R) receptors, to mediate its actions. Activation of AT₁R mediates most of the cardiovascular responses attributed to Ang II (ie, vasoconstriction, mitogenic and hypertrophic effects, fibrosis, inflammation, and fluid retention). In contrast, AT₂R activation may cause opposing physiological responses that are increased in several disease processes.²

Nearly 50 years after the discovery of ACE, a genomic based screening resulted in a characterization of ACE2, thus adding an unexpected twist into the well-known tale of the RAS.^3,4 ACE2 is a carboxypeptidase that cleaves a single residue from Ang I to form Ang-(1-9), which is then converted to Ang-(1-7) by either ACE or neutral endopeptidases.³ This process is less efficient because of the requirement of 2 enzymatic processes. ACE2 also generates Ang-(1-7) from a single residue cleavage of . . . [Full Text of this Article]