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Devil and angel in the renin–angiotensin system: ACE–angiotensin II–AT1 receptor axis vs. ACE2–angiotensin-(1–7)–Mas receptor axis
Open accessAbstract
Recent studies have established a new regulatory axis in the renin-angiotensin system (RAS). In this axis, angiotensin (Ang)-(1-7) is finally produced from Ang I or Ang II by the catalytic activity of angiotensin-converting enzyme 2 (ACE2). Ang-(1-7) shows actions different from those of AT(1) receptor stimulation, such as vasodilatation, natriuresis, anti-proliferation and an increase in the bradykinin-NO (nitric oxide) system. As the catalytic efficiency of ACE2 is approximately 400-fold higher with Ang II as a substrate than with Ang I, this axis is possibly acting as a counter-regulatory system against the ACE/Ang II/AT(1) receptor axis. The signaling pathway of the ACE2-Ang-(1-7) axis has not yet been totally and clearly understood. However, a recent report suggests that the Mas oncogene acts as a receptor for Ang-(1-7). Intracellular signaling through Mas is not clear yet. Several factors such as Akt phosphorylation, protein kinase C activation and mitogen-activated protein (MAP) kinase inhibition seem to be involved in this signaling pathway. Further investigations are needed to clarify the regulation and mechanism of action of ACE2 and Ang-(1-7). However, this second axis through ACE2 and Ang-(1-7) in RAS can be an important target for the therapy of cardiovascular and metabolic disorders.
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“ACE2 on endothelial cells of the arteries, arterioles, and venules of the heart and kidney determines its ability to regulate vascular function and blood pressure, as reviewed previously.”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [53]
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Metadata
- Authors
- Iwai, M., & Horiuchi, M.
- Affiliations
- Ehime University (JP)
- Corresponding author
- Horiuchi, Masatsugu
- Venue
- Hypertension Research
- Published
- 2009-05-22
- Volume
- 32
- Issue
- 7
- Pages
- 533-536
- ISSN
- 0916-9636 (ISSN-L)
- 1348-4214
- PMC
- PMC7091931
- OpenAlex
- W2067142583
- Cited by
- 296
- References
- 37
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 11 · 2023: 20 · 2022: 21 · 2021: 29 · 2020: 29 · 2019: 12 · 2018: 14 · 2017: 10 · 2016: 17 · 2015: 27 · 2014: 19 · 2013: 19 · 2012: 23
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Hypertension Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Hematology › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- renin-angiotensin system, angiotensin-(1-7), angiotensin-converting enzyme 2, Mas receptor, angiotensin II type 1 receptor, angiotensin II, vasodilation, sodium excretion, Akt phosphorylation, protein kinase C, MAP kinase inhibition, cardiovascular disease treatment
- MeSH terms
- Angiotensin-Converting Enzyme 2, Proto-Oncogene Mas, Angiotensin I, Animals, Humans, Peptidyl-Dipeptidase A, Peptide Fragments, Proto-Oncogene Proteins, Renin-Angiotensin System, Signal Transduction, Receptors, G-Protein-Coupled, Receptor, Angiotensin, Type 1
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