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 [PMID: 40546676 DOI: 10.5493/wjem.v15.i2.100748]
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03560591
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April 24, 2025, 13:42
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Reader Comments:
The manuscript 'MicroRNA-155 modulation by renin-angiotensin system inhibitors may underlie their enigmatic role in COVID-19' by Konstantinos I Papadopoulos, Alexandra Papadopoulou and Tar Choon Aw addresses the problem of personalized therapy of COVID-19. The authors rightly point out that agents that inhibit the activity of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitors and AT1R antagonists, can have opposite effects from protective to harmful on the course of the disease, and that worsening of symptoms is seen predominantly in the elderly, in patients with type 2 diabetes, cardiovascular and renal disease, and in some other comorbidities. The authors hypothesise that the negative effects of inhibitors of RAS activity are due to their induced dysregulation of erythropoietin secretion and decreased miRNA-155 levels. The paper cites two references to studies that found a decrease in miRNA-155 following exposure to RAS inhibitors. In conclusion, it is suggested that mineralocorticosteroid receptor antagonists and L-type calcium channel blockers may be preferable to RAS inhibitors in elderly patients and in some comorbidities characterised by reduced baseline miRNA-155 levels. However, a number of the points made by the authors need to be thoroughly tested in further studies, as there is evidence of increased miRNA-155 levels in COVID-19 patients (Asadpour-Behzadi et al, 2023, Haroun et al, 2022), reduced severity of cytokine storm in miRNA-155 knockout animals (Soni et al, 2025) and positive correlation of miRNA-155 levels with inflammatory markers in COVID-19 patients (AL-Nuaimi AL-azzawi, 2025). However, these data do not exclude the possibility that optimal elevation of miRNA-155 levels may be protective, as has been shown in patients with coronary artery disease (Zhu et al., 2014, Ban et al., 2023). Given that miRNA-155 regulates the activity of more than 200 genes, such a non-linear dependence of its effects on levels and physiological characteristics of the organism seems legitimate. The article thus raises a pressing issue that will undoubtedly require further research.
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