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(Circulation Research. 2006;98:887.)
© 2006 American Heart Association, Inc.

Reviews

Signaling by the Angiotensin-Converting Enzyme

Ingrid Fleming

From the Vascular Signalling Group, Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.

Correspondence to Ingrid Fleming, PhD, Vascular Signalling Group, Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. E-mail fleming{at}em.uni-frankfurt.de

This Review is part of a thematic series on Angiotensin-Converting Enzyme, which includes the following articles:

Six Truisms Concerning ACE and the Renin-Angiotensin System Educed from the Genetic Analysis of Mice

ACE II in the Heart and the Kidney

Signaling by the Angiotensin-Converting Enzyme

ACE Polymorphisms

ACE and Vascular Remodeling
Rudi Busse Editors

Inhibition of the angiotensin-converting enzyme (ACE) protects against the progression of several cardiovascular diseases. Because of its dual role in regulating angiotensin II and bradykinin levels, the positive clinical effects of ACE inhibitors were thought to be the consequence of concomitant reductions in the production of angiotensin II and the degradation of bradykinin. Recent evidence suggests that some of the beneficial effects of ACE inhibitors on cardiovascular function and homeostasis can be attributed to novel mechanisms. These include the accumulation of the ACE substrate N-acetyl-seryl-aspartyl-lysyl-proline, which blocks collagen deposition in the injured heart, as well as the activation of an ACE signaling cascade that involves the activation of the kinase CK2 and the c-Jun N-terminal kinase in endothelial cells and leads to changes in gene expression. Moreover, at least one other ACE homologue (ACE2) is proposed to counteract the detrimental effects associated with the activation of the classical renin-angiotensin system. These data reveal hitherto unexpected levels of internal regulation of the renin-angiotensin system.

Key Words: ACEangiotensin II • basic science • c-Jun NH2-terminal kinase • macrophages • signal transduction

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