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Eje Renina Angiotensina, Enzima Convertidora de Angiotensina 2 y Coronavirus / Renin Angiotensin Axis, Angiotensin Converting Enzyme 2 and Coronavirus
Cano, F; Gajardo, M; Freundlich, M.
  • Cano, F; Hospital Luis Calvo Mackenna. Santiago. CL
  • Gajardo, M; Universidad de Chile. Facultad de Medicina. Santiago. CL
  • Freundlich, M; Escuela de Medicina Miller. Miami. US
Rev. chil. pediatr ; 91(3): 330-338, jun. 2020. graf
Article in Spanish | LILACS | ID: biblio-1126169
RESUMEN
Resumen El sistema renina angiotensina aldosterona (SRAA) es el principal regulador del volumen plasmático, manteniendo la homeostasis cardiovascular e hidrosalina. En la vía clásica, la enzima convertidora de angiotensina (ECA) genera Angiotensina II (AngII), de potente efecto inflamatorio y vasoconstrictor. Esta vía clásica es a su vez regulada por la ECA2, que convierte AngII a Ang 1-7, cuyas acciones vaso dilatadoras y antiinflamatorias dan balance a los efectos de AngII. La ECA2 se ha relacionado con la patogenia de infecciones respiratorias como el virus respiratorio sincicial y el síndrome respiratorio agudo grave por coronavirus (SARS-CoV y SARS-CoV-2). Estudios recientes han demostrado que la ECA2 corresponde al principal receptor del SARS-CoV-2, que en conjunto con otros receptores como la serin proteasa TMPRSS2, permiten la fijación, fusión y entrada del virus a la célula huésped. En animales infectados por SARS-CoV se produce una caída de la concentración tisular de ECA2 y Ang 1-7, con la consiguiente sobreexpresión de AngII, y sus efectos vasoconstrictores e inflamatorios. Experimentos con ECA2 recombinante han mostrado un efecto protector frente a la sobreexpresión del SRAA en animales infectados por SARS-CoV, efecto similar al demostrado con el uso de bloquea- dores del receptor de AngII, AT1. La evidencia sobre el rol protector de ECA2 parece respaldar las recomendaciones respecto a no suspender estos medicamentos en la infección SARS-CoV-2. En este artículo presentamos el conocimiento actual sobre el rol del SRAA en la infección por SARS-CoV, a partir de conceptos fisiopatológicos, bases moleculares, y evidencia experimental y clínica.
ABSTRACT
Abstract The renin-angiotensin-aldosterone system (RAAS) is the main plasma volume regulator, which maintains cardiovascular and hydrosaline homeostasis. In the classical pathway, the angiotensin converting enzyme (ACE) generates Angiotensin II (AngII), which is powerfully inflammatory and vasoconstrictive. This classical pathway is also regulated by ACE2, which converts AngI to Ang 1-9, and degrades AngII to Ang 1-7, whose vasodilatory and anti-inflammatory functions balance out the effects of AngII. ACE2 has been associated with the pathogenesis of respiratory infections such as RSV and severe acute respiratory syndrome coronavirus (SARS-CoV and SARS-CoV-2). Recent studies have shown that ACE2 corresponds to the main SARS-CoV-2 receptor, which together with other receptors such as the TMPRSS2, allows the virus to attach, fuse, and enter the host cell. These studies have shown that in animals infected with coronavirus there is a drop in tissue concentration of ACE2 and Ang 1-7, leading to overexpression of AngII and its vasoconstrictive and inflammatory effects. Experiments with recombinant ACE2 have shown a protective effect against overexpression of RAAS in coronavirus-infected animals, which is similar to that demonstrated with the use of AnglI receptor blockers (AT1). Evidence on the protective role of ACE2 seems to support the recommendations re garding not discontinuing these drugs in COVID-19 infection. In this article, we present the current knowledge about the role of RAAS in coronavirus infection, based on physiopathological concepts, molecular bases, and experimental and clinical evidence.
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Full text: Available Index: LILACS (Americas) Main subject: Pneumonia, Viral / Coronavirus Infections / Peptidyl-Dipeptidase A / Betacoronavirus Type of study: Practice guideline Limits: Animals / Humans Language: Spanish Journal: Rev. chil. pediatr Journal subject: Pediatrics Year: 2020 Type: Article Affiliation country: Chile / United States Institution/Affiliation country: Escuela de Medicina Miller/US / Hospital Luis Calvo Mackenna/CL / Universidad de Chile/CL

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Full text: Available Index: LILACS (Americas) Main subject: Pneumonia, Viral / Coronavirus Infections / Peptidyl-Dipeptidase A / Betacoronavirus Type of study: Practice guideline Limits: Animals / Humans Language: Spanish Journal: Rev. chil. pediatr Journal subject: Pediatrics Year: 2020 Type: Article Affiliation country: Chile / United States Institution/Affiliation country: Escuela de Medicina Miller/US / Hospital Luis Calvo Mackenna/CL / Universidad de Chile/CL