Working outside the system: an update on the unconventional behavior of the renin-angiotensin system components.

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TitleWorking outside the system: an update on the unconventional behavior of the renin-angiotensin system components.
Publication TypeJournal Article
Year of Publication2005
AuthorsKurdi, M, De Mello, W, Booz, GW
JournalInt J Biochem Cell Biol
Volume37
Issue7
Pagination1357-67
Date Published2005 Jul
ISSN1357-2725
KeywordsAngiotensin II, Angiotensinogen, Animals, Carboxypeptidases, Humans, Peptidyl-Dipeptidase A, Receptor, Angiotensin, Type 1, Receptor, Angiotensin, Type 2, Renin, Renin-Angiotensin System, Signal Transduction
Abstract

The renin-angiotensin system (RAS) plays an important role in regulating arterial pressure, blood volume, thirst, cardiac function, and cellular growth. Both a circulating and multiple tissue-localized systems have been identified, and are generally portrayed as a series of reactions that occur sequentially with a single outcome: angiotensinogen is cleaved by renin to form angiotensin I, which in turn is processed by angiotensin-converting enzyme (ACE) to angiotensin II, which then activates either the AT1 or the AT2 plasma membrane receptor. Evidence has emerged, however, showing that some RAS components play important roles outside of this canonical scheme. This article provides an overview of some recently identified extra-system functions. In addition to forming angiotensin II, ACE is a multifunctional enzyme equally important in the metabolism of vasodilator and antifibrotic peptides. As the membrane-bound form, ACE functions as a "receptor" that initiates intracellular signaling leading to gene expression. Both angiotensin I and II may lead to actions that are independent of, or even oppose, those of the RAS via their metabolism by the novel ACE-homologue ACE2. The two angiotensin II receptor types have ligand-independent roles that influence cellular signaling and growth, some of which may result from the ability to form hetero-dimers with other 7-transmembrane receptors. Finally, intracellular angiotensin II has been demonstrated to have actions on cell-communication, gene expression, and cellular growth, through both receptor-dependent and independent means. A greater understanding of these extra-system functions of the RAS components may aid in the development of novel treatments for hypertension, myocardial ischemia, and heart failure.

DOI10.1016/j.biocel.2005.01.012
Alternate JournalInt. J. Biochem. Cell Biol.
PubMed ID15833268
Grant ListGM 61838 / GM / NIGMS NIH HHS / United States
NIH HL 34148 / HL / NHLBI NIH HHS / United States