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Abstract <p>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 <i>MAS</i>1 expression in both advanced age (<i>P</i> = 0.03) and the need for oxygen supplementation (<i>P</i> = 0.04). Additionally, reduced <i>ACE</i> expression was associated with worse mortality outcomes (<i>P</i> = 0.01). Notably, <i>ACE2</i> and <i>TMPRSS</i>2 expression was significantly decreased (<i>P</i> &lt; 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 (<i>P</i> = 0.005), miR-let-7 (<i>P</i> = 0.01), and miR-122 (<i>P</i> = 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.</p> Clinical trial <p>Not applicable</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月24日

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  • 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

摘要

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