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.
“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]
The section “Roles of ACE2, Ang-(1–7) and the Mas axis” (page not provided) says ACE2 is highly expressed in the heart and kidney and describes an ACE2-dependent pathway associated with vasodilation and lower blood pressure. It does not locate ACE2 on endothelial cells of arteries, arterioles, or venules, or establish that this specific location determines its vascular effects. (LLM, conf=0.86)
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- 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 › Genetics › 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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