Renin-angiotensin system blockade on angiotensin-converting enzyme 2 and TMPRSS2 in human type II pneumocytes

Silva, Mauro G; Falcoff, Nora; Corradi, Gerardo R.; Alfie, José; Seguel, Rolando F.; Tabaj, Gabriela; Iglesias, Laura I.; Núñez, Margarita Ostrowski de; Guman, Gabriela R.; Gironacci, Mariela M.

doi:10.1016/j.lfs.2022.120324

Cited by 7 publications

(5 citation statements)

References 61 publications

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“…In agreement, sACE2 levels during COVID-19 did not differ depending on the presence of risk factors for severe COVID-19 infection (with the exception of male sex) and were not affected by RAS inhibition [29] . Accordingly, we have recently reported that ACEI/ARB treatment did not modify ACE2 protein expression in type II pneumocytes [12] which are key cells for lung homeostasis. In contrast, a report investigating ACE2 activity in plasma of hypertensive COVID-19 patients who were not experiencing severe COVID-19, found an increase in sACE2 activity under ACEI treatment compared to non-medicated COVID-19 people though with a smaller sample size (n = 9–10) [10] .…”

Section: Discussionmentioning

confidence: 92%

“…An increased sACE2 may reflect higher ACE2 expression, ACE2 shedding or both in those patients. However, we have recently shown that RAS blockade did not modify ACE2 protein expression in human type II pneumocytes, which are key cells for lung homeostasis, of subjects under ACEI treatment [12] . Here, we evaluated plasmatic sACE2 protein levels and enzymatic activity and Ang II and Ang-(1−7) levels in patients hospitalized with COVID-19 compared to healthy subjects.…”

Section: Introductionmentioning

confidence: 84%

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

Silva

Corradi

Duhalde

et al. 2022

Biomedicine & Pharmacotherapy

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 84%

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

Silva

Corradi

Duhalde

et al. 2022

Biomedicine & Pharmacotherapy

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“…Proteins in the supernatant were quantified. The supernatant was subsequently lyophilized and Ang extraction and recovery was performed as described elsewhere [28]. Each sample was corrected for each recovery.…”

Section: Cardiac Expression Of Ang II and Ang-(1-7)mentioning

confidence: 99%

“…Ang II level was quantified by radioimmunoassay using Anglabelled as described previously. Results were expressed as pg/mg tissue [28].…”

Section: Cardiac Expression Of Ang II and Ang-(1-7)mentioning

confidence: 99%

Genetic Deletion of Galectin-3 Exacerbates Age-Related Myocardial Hypertrophy and Fibrosis in Mice

Estevez

Betazza

Miksztowicz

et al. 2022

Cell Physiol Biochem

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Background/Aims: Aging is accompanied by progressive and adverse cardiac remodeling characterized by myocardial hypertrophy, fibrosis, and dysfunction. We previously reported that galectin-3 (Gal-3) is a critical regulator of inflammation and fibrosis associated with hypertensive heart disease and myocardial infarction. Nevertheless, the role and mechanism of Gal-3 in age-related cardiac remodeling have not been previously investigated. We hypothesized that Gal-3 plays a critical role in cardiac aging and that its deficiency exacerbates the underlying mechanisms of myocardial hypertrophy and fibrosis. Methods: Male C57BL/6 (control) (n=24) and Gal-3 knockout (KO) (n=29) mice were studied at 24 months of age to evaluate the role of Gal-3 in cardiac aging. We assessed 1) survival rate; 2) systolic blood pressure (SBP) by plethysmography; 3) myocardial hypertrophy, apoptosis, and fibrosis by quantification of histological and immunohistochemical analysis; 4) cardiac expression of angiotensin (Ang) II, Ang (1–7) by Radioimmunoassay; 5) transforming growth factor-β (TGF-β), sirtuin (SIRT) 1, SIRT 7 and metalloproteinase 9 (MMP-9) by RT-qPCR and 6) ventricular remodeling and function by echocardiography. Results: We found that aged Gal-3 KO mice had a lower survival rate and exhibited exacerbated myocardial hypertrophy and fibrosis without changes in SBP. Similarly, myocardial apoptosis and MMP-9 mRNA expression was significantly increased in the hearts of Gal-3 KO mice compared to controls. Additionally, cardiac Ang II and TGF-β expression were higher in aged Gal-3 KO mice while SIRT1 and SIRT7 expression were reduced. Conclusion: Our findings strongly suggest that Gal-3 is involved in age-related cardiac remodeling by regulating critical mechanisms associated with the development of pathological hypertrophy. The gene deletion of Gal-3 reduced the lifespan and markedly increased age-dependent mechanisms of myocardial hypertrophy, apoptosis, and fibrosis, including Ang-II, TGF-β, and MMP-9. At the same time, there was diminished cardiac-specific expression of SIRT1 and SIRT7, which are extensively implicated in delaying age-dependent cardiomyopathies.

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“…Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the expression of ACE2, resulting in concerns that patients with COVID-19 who are receiving these agents may be at increased risk of severe disease [5][6][7]. However, some recent studies concluded that ACEIs and ARBs do not modify the expression ACE2 and that they do not increase the replication of SARS-CoV-2 [8,9]. Moreover, contrary to the hypnotized negative effects of ACEIs and ARBs on COVID-19 patients, there are conflicting data that they might be beneficial.…”

Section: Introductionmentioning

confidence: 99%

Relation Between Renin–Angiotensin–Aldosterone System Inhibitors and COVID-19 Severity

Alhaddad¹,

Almulaify²,

Alwesaibi³

et al. 2022

Cureus

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Background: Angiotensin-converting enzyme 2 (ACE2) receptor serves as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, to enter the lungs. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the expression of ACE2, resulting in concerns that patients with COVID-19 who are receiving these agents may be at increased risk of severe disease. This study was conducted to further investigate the effects of ACEIs and ARBs on the severity of COVID-19 in hospitalized hypertensive patients.Methods: The study was a retrospective observational study. The medical records of all adult hypertensive patients who were hospitalized at Dammam Medical Complex (DMC) between March 1, 2020, and December 31, 2020, due to COVID-19 were reviewed. The hypertensive patients who were receiving ACEIs or ARBs were compared with the other hypertensive patients who were not on ACEIs or ARBs.Results: A total of 148 hypertensive patients were included in the analysis. They consisted of 106 male and 42 female patients (72% and 28%, respectively). Nearly half of the patients were Saudi (75 patients, 50%). A total of 81 patients were in the ACEI/ARB group, and 67 patients were in the control group. There were no differences between the two groups in age, diabetic status, history of chronic kidney disease, initial blood pressure measurements, and initial oxygen requirements, but the control group contained fewer female patients (18% versus 37%) and Saudi patients (36% versus 63%) than the ACEI/ARB group (p-values = 0.017 and 0.002, respectively). The use of ACEIs or ARBs was associated with significant reductions in ICU admission (9% versus 31%, p-value = 0.001), need for intubation (7% versus 28%, p-value = 0.002), and death (2% versus 24%, p-value = 0.000). A significant negative association between the use ACEIs or ARBs and mortality was also observed in the multivariate analysis after the adjustment for the possible confounders, with an odds ratio (OR) of 0.087 and a 95% confidence interval (CI) of 0.017-0.449. Conclusions: ACEIs and ARBs have no adverse effects on the clinical prognosis of COVID-19 patients with hypertension. Their use might be even beneficial and protective, but future larger studies are needed to confirm these effects. In the meanwhile, they should be continued in COVID-19 hypertensive patients unless their use is contraindicated for other reasons (e.g., hypotension, hyperkalemia, or acute kidney injury (AKI)).

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Renin-angiotensin system blockade on angiotensin-converting enzyme 2 and TMPRSS2 in human type II pneumocytes

Cited by 7 publications

References 61 publications

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

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

Genetic Deletion of Galectin-3 Exacerbates Age-Related Myocardial Hypertrophy and Fibrosis in Mice

Relation Between Renin–Angiotensin–Aldosterone System Inhibitors and COVID-19 Severity

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