Modulation of RAAS receptors and miRNAs in COVID-19: implications for disease severity, immune response, and potential therapeutic targets

Modulation of RAAS receptors and miRNAs in COVID-19: implications for disease severity, immune response, and potential therapeutic targets

Abstract The SARS-CoV-2 spike protein interacts with ACE2, a key receptor within the renin-angiotensin-aldosterone system (RAAS), which plays a critical role in maintaining vascular homeostasis, regulating blood pressure, and modulating inflammation. An observational study analyzed the gene expressi...

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Main Authors: Thais Freitas Barreto Fernandes, Jose Henrique Pilotto, Priscila Alves Cezar, Fernanda Heloise Côrtes, Mariza G. Morgado, Carmem Beatriz W. Giacoia-Gripp, Nathalia Beatriz Ramos De Sá, Andressa Da Silva Cazote, Agatha Freixinho Neves, Marcel De Souza Borges Quintana, Maria Pia Diniz Ribeiro, Sandra Wagner Cardoso, Valdiléa G. Veloso, Beatriz Grinsztejn, Dalziza Victalina De Almeida
Format: Article
Language:English
Published: BMC 2025-03-01
Series:BMC Infectious Diseases
Subjects:
SARS-CoV-2
COVID-19
RAAS
ACE2
miRNA
Online Access:https://doi.org/10.1186/s12879-025-10803-y
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Summary:Abstract The SARS-CoV-2 spike protein interacts with ACE2, a key receptor within the renin-angiotensin-aldosterone system (RAAS), which plays a critical role in maintaining vascular homeostasis, regulating blood pressure, and modulating inflammation. An observational study analyzed the gene expression profiles of RAAS receptors and associated miRNAs in 88 hospitalized COVID-19 patients and 20 healthy controls, comparing the acute and post-acute phases to assess their impact on disease severity and recovery. Our findings revealed an association between reduced MAS1 expression in both advanced age (P = 0.03) and the need for oxygen supplementation (P = 0.04). Additionally, reduced ACE expression was associated with worse mortality outcomes (P = 0.01). Notably, ACE2 and TMPRSS2 expression was significantly decreased (P < 0.0001) in individuals requiring oxygen supplementation and in those with diabetes mellitus during both the acute and post-COVID-19 phases, further highlighting the impact of these conditions on RAAS. The miRNA analysis revealed significant downregulation of miR-200c (P = 0.005), miR-let-7 (P = 0.01), and miR-122 (P = 0.03) in acute-phase COVID-19 patients. This dysregulation contributes to the inflammatory response and highlights the interaction between viral entry and immune regulation. These results underscore the significance of the ACE2/Ang-(1–7)/MAS1 axis in inflammation regulation and suggest that targeting this pathway may have therapeutic potential. Our study provides valuable insights into the molecular mechanisms of COVID-19 pathogenesis and identifies the modulation of RAAS receptors and miRNAs as promising biomarkers for disease severity and potential therapeutic interventions. Clinical trial Not applicable
ISSN:1471-2334

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