Quantifying Renin-Angiotensin-System Alterations in COVID-19

Abstract

The renin-angiotensin system (RAS) plays a pivotal role in a wide series of physiological processes, among which inflammation and blood pressure regulation. One of its key components, the angiotensin-converting enzyme 2, has been identified as the entry point of the SARS-CoV-2 virus into the host cells, and therefore a lot of research has been devoted to study RAS dysregulation in COVID-19. Here we discuss the alterations of the regulatory RAS axes due to SARS-CoV-2 infection on the basis of a series of recent clinical investigations and experimental analyzes quantifying, e.g., the levels and activity of RAS components. We performed a comprehensive meta-analysis of these data in view of disentangling the links between the impaired RAS functioning and the pathophysiological characteristics of COVID-19. We also review the effects of several RAS-targeting drugs and how they could potentially help restore the normal RAS functionality and minimize the COVID-19 severity. Finally, we discuss the conflicting evidence found in the literature and the open questions on RAS dysregulation in SARS-CoV-2 infection whose resolution would improve our understanding of COVID-19.

Repressed Ang 1–7 in COVID-19 Is Inversely Associated with Inflammation and Coagulation

“…1 ) ( 7 ). Ang II acts via the Ang II type-1 receptor (AT 1 R) to induce vasoconstriction, inflammatory cytokine production, and extracellular matrix synthesis ( 8 ). Ang II also stimulates adrenal aldosterone production, leading to sodium and fluid retention and an increase in blood pressure ( 9 ).…”

Plasmatic renin-angiotensin system in normotensive and hypertensive patients hospitalized with COVID-19

“…Regarding Ang-(1−7) levels in COVID-19 patients, some reports have shown an increase [6] , [10] , [27] while others a decrease or no change [11] , [19] , [28] . Thus, despite the fact that COVID-19 is associated with an increased ACE2 [6] , [7] , [8] , [9] , [16] , [29] , conflicting results were reported regarding Ang II and Ang-(1−7) levels [30] . Our work showed that even sACE2 activity was increased, the ratio Ang-(1−7)/Ang II was not changed in the plasma of COVID-19 patients, reflecting that the rate of conversion of Ang II into Ang-(1−7) was not modified.…”

“…Furthermore, Ang-(1−7) can be formed not only from Ang II but also from Ang I. Neutral endopeptidase (EC 3.4.24.11, EP 24.11), neprilysin, thimet oligopeptidase (EC 3.4.24.15) and prolyl oligopeptidase (EC 3.4.21.26) cleave the bond at residues Pro 7 -Phe 8 of Ang I, thus generating Ang-(1−7) [30] , [33] . In fact, COVID-19 is associated with low circulating plasma levels of Ang I and Ang-(1−7) [19] .…”

Papaverine, a promising therapeutic agent for the treatment of COVID‐19 patients with underlying cardiovascular diseases (CVDs)

“…Because SARS‐CoV‐2 depends on the use of host cell facilities for survival and replication, understanding host–cellular functions used by the virus would be essential. Given the advances in this area, scientists suggest that the Renin‐Angiotensin System (RAS) and the p38 mitogen‐activated protein kinase (p38 MAPK) pathway are promising targets for the treatment of COVID‐19 (Dean et al, 2021 ; Grimes & Grimes, 2020a ; Pucci et al, 2021 ; Sohag et al, 2020 ). Accordingly, the use of modulators of such cellular pathways is attracting great attention for the treatment of COVID‐19 (Valipour et al, 2021 ).…”