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
. 2020 May 1;318(5):H1080-H1083.
doi: 10.1152/ajpheart.00215.2020. Epub 2020 Mar 30.

Letter to the Editor: Angiotensin-converting enzyme 2: an ally or a Trojan horse? Implications to SARS-CoV-2-related cardiovascular complications

Zaid Abassi  1   2 , Suheir Assady  3 , Emad E Khoury  1 , Samuel N Heyman  4
Affiliations

Letter to the Editor: Angiotensin-converting enzyme 2: an ally or a Trojan horse? Implications to SARS-CoV-2-related cardiovascular complications

Zaid Abassi et al. Am J Physiol Heart Circ Physiol. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig. 1.
Fig. 1.
The initial step after the invasion of Severe Acute Respiratory Syndrome (SARS)-CoV-2 is binding to membranal angiotensin-converting enzyme 2 (ACE2) widely expressed in cardiac cells including endothelial cells, smooth muscle cells in the myocardial vasculature and in cardiac myocytes. ACE2 is responsible for the conversion of ANG II to Ang-(1–7) that exerts beneficial effects on the cardiac tissue such as vasodilation, antifibrosis, and anti-inflammation via Mas receptor (MasR). The binding of SARS-CoV-2 to ACE2 is preceded by furin-mediated exposure of the viral receptor binding protein (RBP) localized to S-glycoprotein (S1 domain of the viral spike). Furin is abundant in the heart both intracellulary and in the circulation as a free enzyme, making it a key factor in the uncovering of RBP and eventually in SARS-CoV-2 transmission. In addition, furin enhances the affinity of the virus to ACE2 by not only exposing the viral binding site on S1 domain but also revealing the effusion site on the S2 domain in the viral spike. Consequently, the virus undergoes endocytosis and massive replication accompanied by profound activation by cathespsin L (CatL) and the abundant intracellular furin. The activated intracellular SARS-CoV-2 undergoes exocytosis where it binds again to ACE2 elsewhere, thus creating a vicious feed-forward devastating cycle. Importantly, heart failure is characterized by enhanced expression of myocardial ACE2, which is further upregulated by ACE-I, angiotensin receptor blockers (ARBs), and mineralocorticoid-receptor (MR) antagonists, thus sensitizing ACE2 expressing target organs to SARS-CoV-2. ADAM metallopeptidase domain 17 (ADAM 17) is responsible for shading of ACE2, a process stimulated by ANG II type 1 receptors (AT1-R) and may explain why renin-angiotensin-aldosterone system inhibitors augment ACE2 expression. ER, endoplasmic reticulum.
See this image and copyright information in PMC

References

    1. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, Lee M. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA. 2020. March 19 [Epub ahead of print]. doi: 10.1001/jama.2020.4326. - DOI - PMC - PubMed
    1. Burrell LM, Risvanis J, Kubota E, Dean RG, MacDonald PS, Lu S, Tikellis C, Grant SL, Lew RA, Smith AI, Cooper ME, Johnston CI. Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J 26: 369–375, 2005. doi: 10.1093/eurheartj/ehi114. - DOI - PubMed
    1. Clarke NE, Turner AJ. Angiotensin-converting enzyme 2: the first decade. Int J Hypertens 2012: 307315, 2012. doi: 10.1155/2012/307315. - DOI - PMC - PubMed
    1. Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-dos-Santos AJ, da Costa J, Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, Chappell MC, Backx PH, Yagil Y, Penninger JM. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417: 822–828, 2002. doi: 10.1038/nature00786. - DOI - PubMed
    1. Danilczyk U, Penninger JM. Angiotensin-converting enzyme II in the heart and the kidney. Circ Res 98: 463–471, 2006. doi: 10.1161/01.RES.0000205761.22353.5f. - DOI - PubMed

MeSH terms

Substances

LinkOut - more resources