Counter-regulatory renin-angiotensin system in hypertension: review and update in the era of COVID-19 pandemic
Open accessAbstract
Cardiovascular disease is the major cause of mortality and disability, with hypertension being the most prevalent risk factor. Excessive activation of the renin-angiotensin system (RAS) under pathological conditions, leading to vascular remodeling and inflammation, is closely related to cardiovascular dysfunction. The counter-regulatory axis of the RAS consists of angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7), angiotensin (1-9), alamandine, proto-oncogene Mas receptor, angiotensin II type-2 receptor and Mas-related G protein-coupled receptor member D. Each of these components has been shown to counteract the effects of the overactivated RAS. In this review, we summarize the latest insights into the complexity and interplay of the counter-regulatory RAS axis in hypertension, highlight the pathophysiological functions of ACE2, a multifunctional molecule linking hypertension and COVID-19, and discuss the function and therapeutic potential of targeting this counter-regulatory RAS axis to prevent and treat hypertension in the context of the current COVID-19 pandemic.
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The role of the RAS in COVID-19 pathophysiology may be more complex than previously thought.
“Our results, and those of other clinical studies, suggests that the role of the RAS in COVID-19 pathophysiology may be more complex than previously thought.9,28”
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Vascular alterations among young adults with SARS-CoV-2
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Identification of a G Protein-coupled Receptor Specifically Responsive to β-Alanine
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Angiotensin-(1–7) prevents diabetes-induced cardiovascular dysfunction
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Molecular Mechanisms of Inhibition of Vascular Growth by Angiotensin-(1-7)
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Molecular Mechanisms Involved in the Angiotensin-(1-7)/Mas Signaling Pathway in Cardiomyocytes
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Angiotensin II Type 2 Receptor–Bradykinin B 2 Receptor Functional Heterodimerization
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ACE2 and vasoactive peptides: novel players in cardiovascular/renal remodeling and hypertension
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Rise in Blood Pressure Observed Among US Adults During the COVID-19 Pandemic
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The Antithrombotic Effect of Angiotensin-(1-7) Involves Mas-Mediated NO Release from Platelets
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Does COVID-19 Cause Hypertension?
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ACE2 Activation Promotes Antithrombotic Activity
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Angiotensin 1-9 and 1-7 Release in Human Heart
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Flagged first, then by citations
Research works printed but not linked: 1
- [352]G. Wirnsberger, V. Monteil, B. Eaton, E. Postnikova, M. Murphy, B. Braunsfeld, I. Crozier, F. Kricek, J. Niederhofer, A. Schwarzbock, H. Breid, A.S. Jimenez, A. Bugajska-Schretter, A. Dohnal, C. Ruf, R. Gugenberger, A. Hagelkruys, N. Montserrat, M.R. Holbrook, C. Oostenbrink, R.H. Shoemaker, A. Mirazimi, J.M. Penninger, Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants, bioRxiv (2021) 459744.
Cited by
Sorted by citations
Lobo, S. M., Plantefève, G., Nair, G., Joaquim Cavalcante, A., Franzin de Moraes, N., Nunes, E., Barnum, O., Berdun Stadnik, C. M., Lima, M. P., Lins, M., et al. (2024) · eClinicalMedicine · doi:10.1016/j.eclinm.2023.102383 · Cited by 27 · see citing works
- Authors
- Chen, H., Peng, J., Wang, T., Wen, J., Chen, S., Huang, Y., & Zhang, Y.
- Affiliations
- Sun Yat-sen University (CN)
- Corresponding author
- Zhang, Yang
- Venue
- Biochemical Pharmacology
- Publisher
- Elsevier BV
- Published
- 2023-02
- Volume
- 208
- Pages
- 115370
- ISSN
- 0006-2952 (ISSN-L)
- PMC
- PMC9721294
- OpenAlex
- W4310726093
- Cited by
- 19
- References
- 441
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 6
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biochemical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CityU Scholars (submittedVersion, cc-by-nc-nd)
- Funders
- Basic and Applied Basic Research Foundation of Guangdong Province (2021B1515020005)
- National Natural Science Foundation of China (82000462)
- Research Grants Council, University Grants Committee (SRFS2021-4S04)
- 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
- hypertension, angiotensin-converting enzyme 2, angiotensin-(1-7), angiotensin-(1-9), alamandine, Mas receptor, angiotensin II type 2 receptor, COVID-19 pandemic, vascular remodeling, cardiovascular inflammation, antihypertensive therapy
- MeSH terms
- Angiotensin-Converting Enzyme 2, COVID-19, Angiotensin I, Humans, Hypertension, Peptide Fragments, Renin-Angiotensin System, Receptors, G-Protein-Coupled, Pandemics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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