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

Silva, Mauro G; Corradi, Gerardo R.; Duhalde, Juan I. Pérez; Núñez, Margarita Ostrowski de; Maiten, Eliana; Maglio, Daniel H. Gonzales; Brizzio, Ana; Salazar, Martín R.; Espeche, Walter G; Gironacci, Mariela M.

doi:10.1016/j.biopha.2022.113201

Cited by 7 publications

(9 citation statements)

References 41 publications

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“…Despite these findings, current research on cACE2 levels and activity in several cohorts of COVID-19 patients has generated controversy. These studies range from very high or high[ 49 , 50 , 52 , 54 , 55 , 57 , 62 ] to unaltered or even decreased cACE2 levels[ 51 , 58 , 60 ] compared to controls. The effect of age and gender on cACE2 was explored, and there was a trend for cACE2 levels to rise with age.…”

Section: Discussionmentioning

confidence: 99%

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Circulating angiotensin converting enzyme 2 and COVID-19

Leowattana¹,

Leowattana²,

Leowattana³

2022

World J Clin Cases

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a widespread outbreak since December 2019. The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019 (COVID-19) by the World Health Organization. Asymptomatic and subclinical infections, a severe hyper-inflammatory state, and mortality are all examples of clinical signs. After attaching to the angiotensin converting enzyme 2 (ACE2) receptor, the SARS-CoV-2 virus can enter cells through membrane fusion and endocytosis. In addition to enabling viruses to cling to target cells, the connection between the spike protein (S-protein) of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2. Blood pressure is controlled by ACE2, which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin (Ang) II to the heptapeptide Ang-(1-7) and free L-Phe. Additionally, Ang I can be broken down by ACE2 into Ang-(1-9) and metabolized into Ang-(1-7). Numerous studies have demonstrated that circulating ACE2 (cACE2) and Ang-(1-7) have the ability to restore myocardial damage in a variety of cardiovascular diseases and have anti-inflammatory, antioxidant, anti-apoptotic, and anti-cardiomyocyte fibrosis actions. There have been some suggestions for raising ACE2 expression in COVID-19 patients, which might be used as a target for the creation of novel treatment therapies. With regard to this, SARS-CoV-2 is neutralized by soluble recombinant human ACE2 (hrsACE2), which binds the viral S-protein and reduces damage to a variety of organs, including the heart, kidneys, and lungs, by lowering Ang II concentrations and enhancing conversion to Ang-(1-7). This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related. Additionally, there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7) axis.

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Section: Discussionmentioning

confidence: 99%

“…In 93 hospitalized COVID-19 patients and 40 healthy people, the levels of plasmatic cACE2 protein, ACE2 enzymatic activity, Ang II, and Ang-(17) were compared by Silva et al [ 60 ]. They also compared the parameters of COVID-19 between normotensive and hypertensive subjects.…”

Section: Circulating Ace2 In Covid-19 Patientsmentioning

confidence: 99%

Circulating angiotensin converting enzyme 2 and COVID-19

Leowattana¹,

Leowattana²,

Leowattana³

2022

World J Clin Cases

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“…Intraassay and inter-assay variability were 13.7 AE 2.3 and 12.4 AE 3.1%, respectively. ACE2 activity was measured using an ACE2-quenched fluorescent substrate (Mca-Ala-Pro-Lys(Dnp)-OH; Enzo Life Sciences) as described [5].…”

Section: Methodsmentioning

confidence: 99%

“…Whole blood was collected into EDTA-tubes containing 0.44 mmol/l o-phenanthroline, 1 mmol/l sodium-para-chloromercuribenzoate and 25 mmol/l EDTA for Ang II and Ang-(1–7) measurement and a separate tube without those inhibitors for ACE2 activity. Angiotensin levels were quantified by radioimmunoassay as described [5]. Intra-assay and inter-assay variability were 13.7 ± 2.3 and 12.4 ± 3.1%, respectively.…”

Section: Methodsmentioning

confidence: 99%

Circulating angiotensin-(1–7) is decreased in patients with isolated nocturnal hypertension

Minetto,

Cuello,

Dominici

et al. 2024

Journal of Hypertension

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Isolated nocturnal hypertension (INHT), defined as nighttime elevated blood pressure (BP) with normal daytime BP assessed by ambulatory BP monitoring, is associated with higher cardiovascular morbidity and mortality. We hypothesized that an alteration in the circulating renin-angiotensin system (RAS) contributes to INHT development. We examined circulating levels of angiotensin (Ang) (1–7) and Ang II and ACE2 activity in 26 patients that met the INHT criteria, out of 50 that were referred for BP evaluation (62% women, 45 ± 16 years old). Those with INHT were older, had a higher BMI, lower circulating Ang-(1–7) (P = 0.002) and Ang II levels (P = 0.02) and no change in ACE2 activity compared to those normotensives. Nighttime DBP was significantly correlated with Ang-(1–7) and Ang II levels. Logistic regression showed significant association in Ang-(1–7) and Ang II levels with INHT. Our study reveals differences in circulating RAS in individuals with INHT.

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“…Blood samples were collected in EDTA-tubes containing 0.44 mmol/L o-phenanthroline, 1 mmol/L Na + para-chloromercuribenzoate and 25 mmol/L EDTA. Samples were centrifuged at 3,000 xg for 20 min at 4℃ and plasma were loaded into SepPak C18 cartridges for angiotensins extraction as previously described [8]. Because angiotensin may not be completely extracted from the cartridge, angiotensin recovery was calculated and corrected for each sample.…”

Section: Ang II and Ang-(1-7) Levels Measurementmentioning

confidence: 99%

Mechanistic approaching study in COVID-19 patients treated with high doses of vitamin D

Silva

Inserra

Mariani

et al. 2023

Exploration of Medicine

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Aim: To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but treated with high doses of vitamin D (vitD). Methods: From the 218 patients recruited (ClinicalTrials.gov NCT04411446), 16 participated in this sub-study and were randomized to a single oral dose of 500,000 IU vitD (n = 10) or placebo (n = 6). Plasmatic Ang II and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10 and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay before and after treatment. Parallel, serum 25-hydroxyvitamin D3 (25-OH vitD) concentrations as vitD status was measured by a chemiluminescence immunoassay. Results: A trend towards an increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treated COVID-19 patients compared to baseline values. There was no difference in Ang II and Ang-(1-7) levels between placebo- and vitD-treated COVID-19 patients. Similar results were obtained with ILs profile. COVID-19 patients showed an increase in the protective component of the RAS which was not improved by vitD treatment. Conclusions: VitD did not improve RAS disbalance in COVID-19. Notwithstanding, the authors visualize that acute treatment with high doses of vitD may show a trend to a decline in inflammatory ILs and an increase in protective markers. Finally, the authors would like to highlight the limitations of this preliminary study, namely the small number of patients and the use of a large single bolus dose of vitD rather than lower daily doses for extended periods with prolonged follow-up times. All these factors need special consideration in the designs of new vitD supplementation trials. All these factors need special consideration in the designs of new vitD supplementation trials (ClinicalTrials.gov identifier: NCT04411446).

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

Cited by 7 publications

References 41 publications

Circulating angiotensin converting enzyme 2 and COVID-19

Circulating angiotensin converting enzyme 2 and COVID-19

Circulating angiotensin-(1–7) is decreased in patients with isolated nocturnal hypertension

Mechanistic approaching study in COVID-19 patients treated with high doses of vitamin D

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