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Physiol Rev. 2018 Jul 1;98(3):1627-1738. doi: 10.1152/physrev.00038.2017.

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.

Author information

1
Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University , Philadelphia, Pennsylvania ; Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi ; Department of Pharmacology, Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , Iowa City, Iowa ; and Duke-NUS, Singapore and Department of Medicine, Duke University Medical Center , Durham, North Carolina.

Abstract

The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (AT1R) is believed to mediate most functions of ANG II in the system. AT1R utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between AT1R signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. AT1R remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.

PMID:
29873596
PMCID:
PMC6335102
[Available on 2019-07-01]
DOI:
10.1152/physrev.00038.2017
[Indexed for MEDLINE]

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