Cited by 1,924Renin-Angiotensin System StudiesCardiovascular, Neuropeptides, and Oxidative Stress ResearchEicosanoids and Hypertension Pharmacology

Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system

Mehta, Puja K., Griendling, Kathy K.·2007·American Journal of Physiology-Cell Physiology

Abstract

The renin-angiotensin system is a central component of the physiological and pathological responses of cardiovascular system. Its primary effector hormone, angiotensin II (ANG II), not only mediates immediate physiological effects of vasoconstriction and blood pressure regulation, but is also implicated in inflammation, endothelial dysfunction, atherosclerosis, hypertension, and congestive heart failure. The myriad effects of ANG II depend on time (acute vs. chronic) and on the cells/tissues upon which it acts. In addition to inducing G protein- and non-G protein-related signaling pathways, ANG II, via AT 1 receptors, carries out its functions via MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases [PDGF, EGFR, insulin receptor], and nonreceptor tyrosine kinases [Src, JAK/STAT, focal adhesion kinase (FAK)]. AT 1 R-mediated NAD(P)H oxidase activation leads to generation of reactive oxygen species, widely implicated in vascular inflammation and fibrosis. ANG II also promotes the association of scaffolding proteins, such as paxillin, talin, and p130Cas, leading to focal adhesion and extracellular matrix formation. These signaling cascades lead to contraction, smooth muscle cell growth, hypertrophy, and cell migration, events that contribute to normal vascular function, and to disease progression. This review focuses on the structure and function of AT 1 receptors and the major signaling mechanisms by which angiotensin influences cardiovascular physiology and pathology.

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Registry

Crossref · 10.1152/ajpcell.00287.2006

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233 of 233 references verified0 citation errors · 0 not checkable

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  • Deregulation of Ang II production plays a critical role in the pathogenesis of hypertension.

    “As the major component of the renin-angiotensin-aldosterone system, deregulation of Ang II production plays a critical role in the pathogenesis of hypertension22.”

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Authors
Mehta, P. K., & Griendling, K. K.
Affiliations
Emory University (US)
Venue
American Journal of Physiology-Cell Physiology
Published
2007-01
Volume
292
Issue
1
Pages
C82-C97
ISSN
  • 0363-6143 (ISSN-L)
  • 1522-1563
OpenAlex
W2156835140
Cited by
1,924
References
233
Citations by year
2026: 49 · 2025: 61 · 2024: 69 · 2023: 101 · 2022: 93 · 2021: 116 · 2020: 94 · 2019: 100 · 2018: 102 · 2017: 104 · 2016: 83 · 2015: 114 · 2014: 110 · 2013: 122 · 2012: 141
FWCI
13.44
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Cell Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (HL 58000, HL38206, HL70115, P01HL058000)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords
angiotensin II, renin-angiotensin system, angiotensin II type 1 receptor, signal transduction, mitogen-activated protein kinase, receptor tyrosine kinase, non-receptor tyrosine kinase, NADPH oxidase, reactive oxygen species, focal adhesions, extracellular matrix, vascular inflammation, endothelial dysfunction, atherosclerosis, hypertension, congestive heart failure, vasoconstriction, blood pressure regulation, smooth muscle cell hypertrophy
MeSH terms
Angiotensin II, Animals, Cardiovascular Diseases, Cardiovascular Physiological Phenomena, Humans, Renin-Angiotensin System, Structure-Activity Relationship, Vascular Diseases, Signal Transduction, Receptor, Angiotensin, Type 2, Receptor, Angiotensin, Type 1

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