Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2020 Aug;43(8):837-840.
doi: 10.1038/s41440-020-0478-1. Epub 2020 May 20.

Potential differential effects of renin-angiotensin system inhibitors on SARS-CoV-2 infection and lung injury in COVID-19

Masato Furuhashi  1 , Norihito Moniwa  2 , Hideki Takizawa  3 , Nobuyuki Ura  4 , Kazuaki Shimamoto  5
Affiliations
Editorial

Potential differential effects of renin-angiotensin system inhibitors on SARS-CoV-2 infection and lung injury in COVID-19

Masato Furuhashi et al. Hypertens Res. 2020 Aug.
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Possible associations of the renin-angiotensin system with SARS-CoV-2 infection and lung injury caused by SARS-CoV-2. Angiotensin-converting enzyme (ACE) converts angiotensin I (Ang I) to angiotensin II (Ang II). Ang II signaling leads to organ damage, such as lung injury, by promoting inflammation and fibrosis through the Ang II type 1 receptor (AT1R) and has opposing effects through the Ang II type 2 receptor (AT2R). Angiotensin-converting enzyme 2 (ACE2) converts Ang II to Ang-(1–7) and Ang I to Ang-(1–9). Ang-(1–7) signaling attenuates the effects of inflammation and fibrosis through the Mas receptor (Mas-R). It has been suggested that ACE2 is upregulated by some ACE inhibitors (ACEIs) and AT1R blockers (ARBs). ACE2 is also a receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2-binding SARS-CoV-2 is internalized by endocytosis into the cell, and membrane-anchored ACE2 on the cell surface is downregulated. Downregulation of ACE2 promotes organ damage through activation of the ACE/Ang II/AT1R pathway and deactivation of the ACE2/Ang-(1–7)/Mas-R pathway. Another mechanism of SARS-CoV-2 infection is transmembrane protease serine 2 (TMPRSS2)-mediated cleavage of SARS-CoV-2 accompanied by ACE2. ACE2 is also shed from the membrane by a disintegrin and metalloproteinase 17 (ADAM17), and the soluble form of ACE2 may intercept the virus from binding to membrane-anchored ACE2 in the cell plasma membrane. Possible increases in the expression and soluble form of ACE2 induced by RAS inhibitors would have beneficial effects of protection against lung injury and other organ damage but not infection with SARS-CoV-2
See this image and copyright information in PMC

References

    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5. - DOI - PMC - PubMed
    1. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area. JAMA. 2020. 10.1001/jama.2020.6775. - PMC - PubMed
    1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.. doi: 10.1016/S0140-6736(20)30566-3. - DOI - PMC - PubMed
    1. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020. 10.1001/jama.2020.5394. - PMC - PubMed
    1. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020. 10.1001/jama.2020.1585. - PMC - PubMed

Publication types

MeSH terms

Substances