Basic Study
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World J Gastroenterol. Aug 21, 2024; 30(31): 3705-3716
Published online Aug 21, 2024. doi: 10.3748/wjg.v30.i31.3705
Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19
Angus K Jacobs, Steven D Morley, Kay Samuel, Katie Morgan, Lyndsey Boswell, Timothy J Kendall, David A Dorward, Jonathan A Fallowfield, Peter C Hayes, John N Plevris
Angus K Jacobs, Steven D Morley, Katie Morgan, Peter C Hayes, John N Plevris, Hepatology Laboratory, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom
Kay Samuel, Scottish National Blood Transfusion Service, Jack Copland Centre, Edinburgh EH14 4BE, United Kingdom
Lyndsey Boswell, Timothy J Kendall, Jonathan A Fallowfield, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, United Kingdom
Timothy J Kendall, David A Dorward, Edinburgh Pathology, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom
Author contributions: Jacobs AK and Plevris JN conceptualised and planned the research and all authors contributed to the study design; Jacobs AK, Morgan K, and Boswell L performed the experiments and acquired the data; Kendall TJ and Dorward DA contributed new reagents and analytic tools; Jacobs AK wrote the original draft manuscript; Morley SD, Samuel K and Plevris JN revised the manuscript. All authors contributed to analysis and validation of the data and interpretation of the research. All authors reviewed original and subsequent drafts, provided feedback and approved the final version of the manuscript.
Supported by University of Edinburgh Hepatology Laboratory Internal Funding; and the Liver Endowment Funds of the Edinburgh & Lothian Health Foundation.
Institutional review board statement: The study was conducted according to the guidelines of the Declaration of Helsinki and in compliance with the Human Tissue Act 2004. Anonymised human tissue samples were obtained from the Lothian NRS Human Annotated Bioresource under East of Scotland Research Ethics Service REC 1 approval (20/ES/0061 IRAS 281531) and the ‘Inflammation in COVID-19: Exploration of Critical Aspects of Pathogenesis’ (ICECAP) study under East of Scotland Research Ethics Service REC 1 approval (16/ES/0084). IRAS data website: https://www.hra.nhs.uk/planning-and-improving-research/applicationsummaries/research-summaries/.
Conflict-of-interest statement: No conflict of interest has been declared by any of the authors impacting on the work presented in this manuscript.
Data sharing statement: Data obtained from the ICECAP study and are available from Prof David A. Dorward with the permission of the ICECAP Consortium (https://www.ed.ac.uk/inflammation-research/research/icecap).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Angus K Jacobs, BSc, Postgraduate Scientist, Hepatology Laboratory, University of Edinburgh, Chancellor’s Building, Edinburgh BioQuarter, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom. angus.jacobs@ed.ac.uk
Received: March 18, 2024
Revised: July 3, 2024
Accepted: July 30, 2024
Published online: August 21, 2024
Processing time: 148 Days and 6.5 Hours
Core Tip

Core Tip: There has been much recent interest in angiotensin-converting expression enzyme 2 (ACE2) as the fulcrum of the ‘anti-inflammatory’ renin-angiotensin system pathway because severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), targets ACE2 for viral attachment and host cell invasion. Previously ACE2 mRNA has been measured in metabolic dysfunction-associated steatotic liver disease (MASLD) and COVID-19 infection but, uniquely, we used immunohistochemistry, alongside measurement of fibrosis and lipid, to show that ACE2 protein levels and hepatic lipid content are correlated across the MASLD pathophysiological spectrum and in COVID-19 patients showing evidence of liver injury. Hepatic lipids are also associated with the presence of SARS-CoV-2 virus in the liver suggesting a possible functional link.