Review
ACE2 Down-Regulation May Act as a Transient Molecular Disease Causing RAAS Dysregulation and Tissue Damage in the Microcirculatory Environment Among COVID-19 Patients

https://doi.org/10.1016/j.ajpath.2021.04.010Get rights and content
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Severe acute respiratory syndrome coronavirus 2, the etiologic agent of coronavirus disease 2019 (COVID-19) and the cause of the current pandemic, produces multiform manifestations throughout the body, causing indiscriminate damage to multiple organ systems, particularly the lungs, heart, brain, kidney, and vasculature. The aim of this review is to provide a new assessment of the data already available for COVID-19, exploring it as a transient molecular disease that causes negative regulation of angiotensin-converting enzyme 2, and consequently, deregulates the renin-angiotensin-aldosterone system, promoting important changes in the microcirculatory environment. Another goal of the article is to show how these microcirculatory changes may be responsible for the wide variety of injury mechanisms observed in different organs in this disease. The new concept of COVID-19 provides a unifying pathophysiological picture of this infection and offers fresh insights for a rational treatment strategy to combat this ongoing pandemic.

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Supported by grants from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil) [no. 88882.378587/2019-01]; the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP/SP/Brazil) [no. 2012/23649-0]; and the Fundação de Apoio ao Ensino, Pesquisa e Assistência do HCFMRP-USP (FAEPA/Brazil) [ no. 269/2021; no. 272/2021].

Disclosures: None declared.