Papadopoulos KI, Papadopoulou A, Aw TC. MicroRNA-155 modulation by renin-angiotensin system inhibitors may underlie their enigmatic role in COVID-19. World J Exp Med 2025; 15(2): 100748 [DOI: 10.5493/wjem.v15.i2.100748]
Corresponding Author of This Article
Konstantinos I Papadopoulos, MD, PhD, Chief Physician, Director, Department of R and D, THAI StemLife, 566/3 THAI StemLife Bldg., Soi Ramkhamhaeng 39 (Thepleela 1), Prachaouthit Road, Wangthonglang, Bangkok 10310, Thailand. kostas@thaistemlife.co.th
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Exp Med. Jun 20, 2025; 15(2): 100748 Published online Jun 20, 2025. doi: 10.5493/wjem.v15.i2.100748
MicroRNA-155 modulation by renin-angiotensin system inhibitors may underlie their enigmatic role in COVID-19
Konstantinos I Papadopoulos, Alexandra Papadopoulou, Tar Choon Aw
Konstantinos I Papadopoulos, Department of R and D, THAI StemLife, Bangkok 10310, Thailand
Alexandra Papadopoulou, Department of Occupational and Environmental Health Services, Feelgood Lund, Lund 223-63, Skåne, Sweden
Tar Choon Aw, Department of Laboratory Medicine, Changi General Hospital, Singapore 529889, Singapore
Tar Choon Aw, Department of Medicine, National University of Singapore, Singapore 119228, Singapore
Author contributions: Papadopoulos KI conceived and conceptualized the pathophysiology, designed the letter, drafted the initial manuscript, and reviewed and revised the manuscript; Papadopoulou A performed the literature search, extracted vital information, contributed to the synthesis of the letter, and reviewed and revised the manuscript; Aw TC coordinated and supervised the literature search, made substantial and direct intellectual contributions, and critically reviewed the manuscript for important intellectual content; all authors approved the submitted final manuscript and agree to be accountable for all aspects of the work.
Conflict-of-interest statement: No conflicts of interest are reported by any of the authors.
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: Konstantinos I Papadopoulos, MD, PhD, Chief Physician, Director, Department of R and D, THAI StemLife, 566/3 THAI StemLife Bldg., Soi Ramkhamhaeng 39 (Thepleela 1), Prachaouthit Road, Wangthonglang, Bangkok 10310, Thailand. kostas@thaistemlife.co.th
Received: August 26, 2024 Revised: January 18, 2025 Accepted: February 6, 2025 Published online: June 20, 2025 Processing time: 234 Days and 0.3 Hours
Abstract
Severe acute respiratory coronavirus-2 (SARS-CoV-2) infection course differs between the young and healthy and the elderly with co-morbidities. In the latter a potentially lethal coronavirus disease 2019 (COVID-19) cytokine storm has been described with an unrestrained renin-angiotensin (Ang) system (RAS). RAS inhibitors [Ang converting enzyme inhibitors and Ang II type 1 receptor (AT1R) blockers] while appearing appropriate in COVID-19, display enigmatic effects ranging from protection to harm. MicroRNA-155 (miR-155)-induced translational repression of key cardiovascular (CV) genes (i.e., AT1R) restrains SARS-CoV-2-engendered RAS hyperactivity to tolerable and SARS-CoV-2-protective CV phenotypes supporting a protective erythropoietin (EPO) evolutionary landscape. MiR-155’s disrupted repression of the AT1R 1166C-allele associates with adverse CV and COVID-19 outcomes, confirming its decisive role in RAS modulation. RAS inhibition disrupts this miR-155-EPO network by further lowering EPO and miR-155 in COVID-19 with co-morbidities, thereby allowing unimpeded RAS hyperactivity to progress precariously. Current pharmacological interventions in COVID-19 employing RAS inhibition should consider these complex but potentially detrimental miR-155/EPO-related effects.
Core Tip: The role of renin-angiotensin system (RAS) inhibition in coronavirus disease 2019 (COVID-19) remains enigmatic. Novel insights involving interference of microRNA-155 (miR-155) and erythropoietin (EPO) levels support a detrimental role by RAS inhibitors in the elderly and in co-morbidities. Current pharmacological interventions in COVID-19 employing RAS inhibition should consider these complex but potentially detrimental miR-155 effects. Future research should address the knowledge gap on how RAS inhibition affects miR-155 while therapeutic strategies should focus on pharmacological interventions that restore EPO and miR-155 levels and functionality. The use of tissue specific miRNA analogs could become a reality by then.
