ACE2, ACE, DPPIV, PREP and CAT L enzymatic activities in COVID-19: imbalance of ACE2/ACE ratio and potential RAAS dysregulation in severe cases

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Neves, Raquel Leao ; Branquinho, Jessica ; Arata, Julia Galanakis ; Bittencourt, Clarissa Azevedo ; Gomes, Caio Perez ; Riguetti, Michelle ; da Mata, Gustavo Ferreira ; Fernandes, Danilo Euclides ; Icimoto, Marcelo Yudi ; Kirsztajn, Gianna Mastroianni ; Pesquero, Joao Bosco

• Document type: Journal article
• Source: Inflammation Research; v. 72, n. 8, p. 13-pg., 2023-08-03.

Abstract

Objective and designCirculating enzymatic activity and RAAS regulation in severe cases of COVID-19 remains unclear, therefore we measured the serum activity of several proteases as potential targets to control the SARS-CoV-2 infection.Material or subjects152 patients with COVID-19-like symptoms were grouped according to the severity of symptoms (COVID-19 negative, mild, moderate and severe).MethodsSerum samples of COVID-19 patients and controls were subjected to biochemical analysis and enzymatic assays of ACE2, ACE, DPPIV, PREP and CAT L. One-way ANOVA and multivariate logistic regression analysis were used. Statistical significance was accepted at p < 0.05.ResultsWe detected a positive correlation among comorbidities, higher C-reactive protein (CRP) and D-dimer levels with disease severity. Enzymatic assays revealed an increase in serum ACE2 and CAT L activities in severe COVID-19 patients, while ACE, DPPIV and PREP activities were significantly reduced. Notably, analysis of ACE2/ACE activity ratio suggests a possible imbalance of ANG II/ANG(1-7) ratio, in a positive association with the disease severity.ConclusionOur findings reveal a correlation between proteases activity and the severity of COVID-19. These enzymes together contribute to the activation of pro-inflammatory pathways, trigger a systemic activation of inflammatory mediators, leading to a RAAS dysregulation and generating a significant damage in several organs, contributing to poor outcomes of severe cases. (AU)

• FAPESP's process: 19/01487-7 - Gold Nanoparticles associated to Bromelain-derived Cisteine-Proteases: Structural Characterization and Collagenolytic Activity.
• Grantee: Marcelo Yudi Icimoto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/27198-8 - Establishment of a center of genetic and molecular research for clinical challenges
• Grantee: João Bosco Pesquero
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/05266-5 - Detection and functional characterization of genetic mutations in familial and sporadic focal segmental glomerulosclerosis
• Grantee: Gianna Mastroianni Kirsztajn
• Support Opportunities: Regular Research Grants