Increased circulating levels of angiotensin-(1-7) in severely ill COVID-19 patients

Martins, Ana Luiza Valle; Silva, Filipe Alex da; Bolais-Ramos, Lucas; Oliveira, Gisele Capanema de; Ribeiro, Renata Cunha; Pereira, Danilo Augusto Alves; Annoni, Filippo; Diniz, Mirella Monique Lana; Silva, Thuanny Granato Fonseca; Zivianni, Bruna; Cardoso, Alexandre Carvalho; Martins, Juliana Carvalho; Motta‐Santos, Daisy; Campagnole‐Santos, Maria José; Taccone, Fabio Silvio; Verano‐Braga, Thiago; Santos, Robson Augusto Souza

doi:10.1101/2021.02.01.20232785

Cited by 19 publications

(33 citation statements)

References 11 publications

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“…Patients with severe COVID-19 illness had significantly increased circulating levels of angiotensin 1-7 and decreased angiotensin II [82,83]. The angiotensin 1-7/angiotensin II ratio was 3-fold higher in COVID-19 patients as compared to that in healthy controls, thus suggesting an increased activity of ACE2 or other angiotensin 1-7 forming activity after COVID-19 infection [82]. Although TOP is an important angiotensin 1-7 forming factor, expression or activity of TOP in COVID-19 patients have not been analyzed.…”

Section: Effects Of Top In Intracellular Processing Of Angiotensin 1-7 and Its Potential Involvement In Covid-19 Pathogenesismentioning

confidence: 99%

Section: Effects Of Top In Intracellular Processing Of Angiotensin 1-7 and Its Potential Involvement In Covid-19 Pathogenesismentioning

confidence: 99%

“…Recent studies have found a potential link between angiotensin 1-7 and COVID-19 pathophysiology [82,83]. Patients with severe COVID-19 illness had significantly increased circulating levels of angiotensin 1-7 and decreased angiotensin II [82,83]. The angiotensin 1-7/angiotensin II ratio was 3-fold higher in COVID-19 patients as compared to that in healthy controls, thus suggesting an increased activity of ACE2 or other angiotensin 1-7 forming activity after COVID-19 infection [82].…”

Section: Effects Of Top In Intracellular Processing Of Angiotensin 1-7 and Its Potential Involvement In Covid-19 Pathogenesismentioning

confidence: 99%

“…However, elevated ACE2 expression has been observed in patients with COVID-19 infection [83,104]. One may, thus, expect that TOP may possibly affect ACE2 expression through processing intracellular angiotensin 1-7, therefore affecting vulnerability of the cells of given tissue/organs to SARS-CoV-2 infection [82,83]. Interestingly, Soria-Castro et al [105] recently reported that COVID-19 patients showed increased carboxypeptidase A3 (CPA3), which is also known for its function in converting angiotensin II to angiotensin 1-7 [81].…”

Section: Effects Of Top In Intracellular Processing Of Angiotensin 1-7 and Its Potential Involvement In Covid-19 Pathogenesismentioning

confidence: 99%

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Thimet Oligopeptidase—A Classical Enzyme with New Function and New Form

Liu

Sigman

Bruce

et al. 2021

Immuno

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Peptidases generate bioactive peptides that can regulate cell signaling and mediate intercellular communication. While the processing of peptide precursors is initiated intracellularly, some modifications by peptidases may be conducted extracellularly. Thimet oligopeptidase (TOP) is a peptidase that processes neuroendocrine peptides with roles in mood, metabolism, and immune responses, among other functions. TOP also hydrolyzes angiotensin I to angiotensin 1–7, which may be involved in the pathophysiology of COVID-19 infection. Although TOP is primarily cytosolic, it can also be associated with the cell plasma membrane or secreted to the extracellular space. Recent work indicates that membrane-associated TOP can be released with extracellular vesicles (EVs) to the extracellular space. Here we briefly summarize the enzyme’s classical function in extracellular processing of neuroendocrine peptides, as well as its more recently understood role in intracellular processing of various peptides that impact human diseases. Finally, we discuss new findings of EV-associated TOP in the extracellular space.

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Section: Effects Of Top In Intracellular Processing Of Angiotensin 1-7 and Its Potential Involvement In Covid-19 Pathogenesismentioning

confidence: 99%

Section: Effects Of Top In Intracellular Processing Of Angiotensin 1-7 and Its Potential Involvement In Covid-19 Pathogenesismentioning

confidence: 99%

Section: Effects Of Top In Intracellular Processing Of Angiotensin 1-7 and Its Potential Involvement In Covid-19 Pathogenesismentioning

confidence: 99%

Section: Effects Of Top In Intracellular Processing Of Angiotensin 1-7 and Its Potential Involvement In Covid-19 Pathogenesismentioning

confidence: 99%

See 2 more Smart Citations

Thimet Oligopeptidase—A Classical Enzyme with New Function and New Form

Liu

Sigman

Bruce

et al. 2021

Immuno

View full text Add to dashboard Cite

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“…The observed overactivation of the non-classical RAS axis is expected to yield an increase of circulating Ang-(1-5), obtained by cleavage of Ang-(1-7) by ACE (Figure 1). Yet opposite trends are found for the levels of circulating Ang-(1-5) measured in two studies: a reduction of about 80% in the COVID-19 class with respect to controls [84], or a 100% increase [80] (see Supplementary Table S1).…”

Section: Meta-analysis On Ras Components In Covid-19mentioning

confidence: 76%

Quantifying renin-angiotensin-system alterations in COVID-19

Pucci

Annoni

Santos

et al. 2021

Preprint

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The renin-angiotensin system (RAS) plays a pivotal role in a wide series of physiological processes. 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, so many studies have 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 and experimental analyzes, which, for example, quantify the levels and activity of RAS components, in order to disentangle the links between the impaired RAS functioning and the pathophysiological characteristics of COVID-19. Finally, we discussed the effects of some RAS-targeting drugs, and how they could potentially contribute to restore the normal RAS functionality and minimize COVID-19 severity.

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Patients with severe COVID‐19 have reduced circulating levels of angiotensin‐(1–7): A cohort study

Seyedmehdi

Imanparast

Mohaghegh

et al. 2022

Health Science Reports

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Background and Aims Angiotensin‐converting enzyme 2 (ACE2) acts as a functional receptor for the entry of severe acute respiratory syndrome coronavirus 2 into host cells. Angiotensin (1–7) (Ang (1–7)) obtained from the function of ACE2 improves heart and lung function. We investigated the relationship between Ang (1–7) level and disease severity in patients with coronavirus disease 2019 (COVID‐19). Methods This cohort study was carried out at Masih Daneshvari Hospital in Tehran, Iran from September 2020 to October 2020. To do so, the Ang (1–7) levels of 331 hospitalized COVID‐19 patients with and without underlying disease were measured by ELISA kit. The need for oxygen, intubation, and mechanical ventilation were recorded for all the patients. Results Results showed a significant inverse relationship between the levels of Ang 1–7 and the severity of the disease (needed oxygen, intubation, and mechanical ventilation). According to the results, median (interquartile range) of Ang (1–7) levels was significantly lower in patients who needed oxygen versus those who needed no oxygen (44.50 (91) vs. 82.25 (68), p = 0.002), patients who needed intubation and mechanical ventilation versus those who did not (9.80 (62) vs. 68.70 (102), p < 0.000) and patients hospitalized in an intensive care unit (ICU) than people hospitalized in other wards. We also found that the older patients were more in need of ICU and mechanical ventilation than younger patients. Conclusions Higher levels of Ang (1–7) have been associated with decreased disease severity. Besides this, we perceived that synthetic Ang 1–7 peptides may be useful to treat and reduce the complications of COVID‐19.

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Increased circulating levels of angiotensin-(1-7) in severely ill COVID-19 patients

Cited by 19 publications

References 11 publications

Thimet Oligopeptidase—A Classical Enzyme with New Function and New Form

Thimet Oligopeptidase—A Classical Enzyme with New Function and New Form

Quantifying renin-angiotensin-system alterations in COVID-19

Patients with severe COVID‐19 have reduced circulating levels of angiotensin‐(1–7): A cohort study

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