The DOI matches its Crossref record; 85 of the 85 references it cites were found in a registry or an index.
Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease
Open accessAbstract
Angiotensin-converting enzyme 2 (ACE2) shares some homology with angiotensin-converting enzyme (ACE) but is not inhibited by ACE inhibitors. The main role of ACE2 is the degradation of Ang II resulting in the formation of angiotensin 1–7 (Ang 1–7) which opposes the actions of Ang II. Increased Ang II levels are thought to upregulate ACE2 activity, and in ACE2 deficient mice Ang II levels are approximately double that of wild-type mice, whilst Ang 1–7 levels are almost undetectable. Thus, ACE2 plays a crucial role in the RAS because it opposes the actions of Ang II. Consequently, it has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease where its expression is decreased. Not surprisingly, current therapeutic strategies for ACE2 involve augmenting its expression using ACE2 adenoviruses, recombinant ACE2 or compounds in these diseases thereby affording some organ protection.
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![Figure 2 Increased plaque area accumulation in the aorta of Apoe/Ace2 double KO mice when compared to control Apoe KO mice [5]. *vs control Apoe KO mice P < 0.05.](/paper-figures/a00ddc264d5148bdad0297283ee18404/angiotensin-converting-enzyme-2-ace2-is-a-key-modulator-of-the-renin-angiotensin-figure-2.jpg)
![Figure 4 Reduced ACE2 expression (arrows) in renal cortical tubules of diabetic mice (b) when compared to control mice (a) [27].](/paper-figures/4fcf736818a342e38daaaa1cbec06627/angiotensin-converting-enzyme-2-ace2-is-a-key-modulator-of-the-renin-angiotensin-figure-4.jpg)
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“Decreased expression of ACE2 could mean less potential for SARS-CoV-2 invasion of host cells, and further ACE2 reduction caused by viral entry may exacerbate a heightened proinflammatory response that helps mediate cytokine storm, acute lung injury, and ARDS.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [65]
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“ACE2 is also downregulated in humans with cardiovascular disease and diabetes, which also correlate with severe COVID-1965.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [65]
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Cites
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) · Nature · doi:10.1038/nature02145 · Cited by 5,923
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A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury
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Angiotensin-converting enzyme 2 protects from severe acute lung failure
Imai, Y., Kuba, K., Rao, S., Huan, Y., Guo, F., Guan, B., Yang, P., Sarao, R., Wada, T., Leong-Poi, H., et al. (2005) · Nature · doi:10.1038/nature03712 · Cited by 2,453
A Human Homolog of Angiotensin-converting Enzyme
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Angiotensin-converting enzyme 2 is an essential regulator of heart function
Crackower, M. A., Sarao, R., Oudit, G. Y., Yagil, C., Kozieradzki, I., Scanga, S. E., Oliveira-dos-Santos, A. J., da Costa, J., Zhang, L., Pei, Y., et al. (2002) · Nature · doi:10.1038/nature00786 · Cited by 1,733
Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase
Vickers, C., Hales, P., Kaushik, V. K., Dick, L. R., Gavin, J. M., Tang, J., Godbout, K., Parsons, T. F., Baronas, E., Hsieh, F., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200581200 · Cited by 1,406
Sadoshima, J.-I., Xu, Y., Slayter, H. S., & Izumo, S. (1993) · Cell · doi:10.1016/0092-8674(93)90541-w · Cited by 1,348
Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall.
Daemen, M. J. A. P., Lombardi, D. M., Bosman, F. T., & Schwartz, S. M. (1991) · Circulation Research · doi:10.1161/01.res.68.2.450 · Cited by 738
Research works printed but not linked: 4
- 2000, Circulation Research, 87, E1
- 2002, American Journal of Physiology, 282, H2254
- 1993, Circulation, 87, IV7
- 1994, Hypertension, 23, 869
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COVID-19 and cardiovascular disease
Clerkin, K. J., Fried, J. A., Raikhelkar, J., Sayer, G., Griffin, J. M., Masoumi, A., Jain, S. S., Burkhoff, D., Kumaraiah, D., Rabbani, L., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.046941 · Cited by 1,738
The pivotal link between ACE2 deficiency and SARS-CoV-2 infection
Verdecchia, P., Cavallini, C., Spanevello, A., & Angeli, F. (2020) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2020.04.037 · Cited by 1,237
“[61-63] Several experimental and clinical studies indicate that ACE2 deficiency obtained through deletion or inhibition may be a causative factor for hypertension.”
Bourgonje, A. R., Abdulle, A. E., Timens, W., Hillebrands, J., Navis, G. J., Gordijn, S. J., Bolling, M. C., Dijkstra, G. D. H., Voors, A. A., Osterhaus, A. D. M. E., et al. (2020) · The Journal of Pathology · doi:10.1002/path.5471 · Cited by 1,160
Health benefits of polyphenols: A concise review
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The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management
Abou-Ismail, M. Y., Diamond, A., Kapoor, S., Arafah, Y., & Nayak, L. (2020) · Thrombosis Research · doi:10.1016/j.thromres.2020.06.029 · Cited by 694
Metadata
- Authors
- Tikellis, C., & Thomas, M. C.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Corresponding author
- Tikellis, Chris
- ORCID
- Thomas, M. C.
- Venue
- International Journal of Peptides
- Publisher
- Hindawi Limited
- Published
- 2012-03-20
- Volume
- 2012
- Pages
- 1-8
- ISSN
- 1687-9767 (ISSN-L)
- 1687-9775
- PMC
- PMC3321295
- OpenAlex
- W2082133861
- Cited by
- 624
- References
- 85
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 31 · 2023: 57 · 2022: 87 · 2021: 164 · 2020: 244 · 2019: 7 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 3
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- International Journal of Peptides (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- National Health and Medical Research Council
- 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
- angiotensin-converting enzyme 2, renin-angiotensin system, angiotensin II, angiotensin-(1-7), hypertension, diabetes mellitus, cardiovascular disease, organ protection
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