Cell differentiation and aging is accompanied by depletion of the ACE2 protein

Bártová, Eva; Legartová, Soňa; Krejčí, Jana; Arcidiacono, Orazio Angelo

doi:10.21203/rs.3.rs-39062/v1

Cited by 12 publications

(26 citation statements)

References 18 publications

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“…The expression of these factors in different stem cells was relatively low, but, for example, among cells expressing markers that are specific to the gas-exchanging alveoli, AEPs exhibited higher expression of SARS-CoV-2 entry factors than differentiated AT1 and AT2 cells. These results are in agreement with the observations that cell differentiation is accompanied by depletion of the ACE2 protein 41 .…”

Section: Discussionsupporting

confidence: 93%

Expression of SARS-CoV-2 entry factors in lung epithelial stem cells and its potential implications for COVID-19

Valyaeva

Zharikova

Kasianov

et al. 2020

Sci Rep

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SARS-CoV-2 can infiltrate the lower respiratory tract, resulting in severe respiratory failure and a high death rate. Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection. Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, including Ace2. Thus, stem cells can be potentially infected by SARS-CoV-2, which may lead to defects in regeneration capacity partially accounting for the severity of SARS-CoV-2 infection and its consequences.

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Section: Discussionsupporting

confidence: 93%

Expression of SARS-CoV-2 entry factors in lung epithelial stem cells and its potential implications for COVID-19

Valyaeva

Zharikova

Kasianov

et al. 2020

Sci Rep

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“…Similarly, treatment with the ACE-Inh. lisinopril (100 nM) did not alter ACE2 expression in A549 lung cancer cells ( Bartova, Legartova, Krejci, & Arcidiacono, 2020 ). In another recent study on human alveolar adenocarcinoma (A549) and lung cancer (Calu-3) cell lines, Ang-I (10-1000 nM) and Ang-II (1-100 nM) did not alter ACE2 expression.…”

Section: Cardiovascular Drugs and Ace2mentioning

confidence: 97%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

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The recent emergence of coronavirus disease-2019 (COVID-19) as a global pandemic has prompted scientists to address an urgent need for defining mechanisms of disease pathology and treatment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, employs angiotensin converting enzyme 2 (ACE2) as its primary target for cell surface attachment and likely entry into the host cell. Thus, understanding factors that may regulate the expression and function of ACE2 in the healthy and diseased body is critical for clinical intervention. Over 66% of all adults in the United States are currently using a prescription drug and while earlier findings have focused on possible upregulation of ACE2 expression through the use of renin angiotensin system (RAS) inhibitors, mounting evidence suggests that various other widely administered drugs used in the treatment of hypertension, heart failure, diabetes mellitus, hyperlipidemias, coagulation disorders, and pulmonary disease may also present a varied risk for COVID-19. Specifically, we summarize mechanisms on how heparin, statins, steroids and phytochemicals, besides their established therapeutic effects, may also interfere with SARS-CoV-2 viral entry into cells. We also describe evidence on the effect of several vitamins, phytochemicals, and naturally occurring compounds on ACE2 expression and activity in various tissues and disease models. This comprehensive review aims to provide a timely compendium on the potential impact of commonly prescribed drugs and pharmacologically active compounds on COVID-19 pathology and risk through regulation of ACE2 and RAS signaling.

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“…34,35 Accordingly, aging caused a reduction in ACE2 expression in various organs of mice, being the lowest in the lungs. 38,39 We observed that smoking and RAS blockade in uence on the percentage of human lung ACE2expressing type II pneumocytes: the percentage of ACE2-expressing type II pneumocytes was similar between untreated never smokers or smokers but increased in smokers under RAS blockade. Furthermore, we also found that the greater percentage of subjects that exhibited higher ACE2 protein levels was that of older smokers and former smokers.…”

Section: Discussionmentioning

confidence: 80%

Renin-Angiotensin System Blockade Influences ACE2 in Human Type II Pneumocytes

Silva

Falcoff

Corradi

et al. 2021

Preprint

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Rationale—Angiotensin converting enzyme (ACE) 2 and the transmembrane protease serine 2 (TMPRSS2) are key for cellular entry of the type 2 coronavirus that causes severe acute respiratory syndrome (SARS-CoV2), the etiological agent of coronavirus-19 disease (COVID-19). There has been a growing concern that renin-angiotensin system (RAS) blockade with ACE inhibitors (ACEIs) or type 1 angiotensin (Ang II) receptor blockers (ARBs) increases ACE2 expression and then elevate patient susceptibility to SARS-CoV-2. However, evidence about RAS blockade and ACE2 in human lung are lacking.Objective– To investigate RAS blockade on ACE2 and TMPRSS2 in type II pneumocytes of human lung parenchymal of untreated and ACEI/ARB-treated hypertensive subjects.Methods and Results– ACE2 and TMPRSS2 protein expression were measured by immunohistochemistry. We found that smoking and RAS blockade influence on the percentage of human ACE2-expressing type II pneumocytes (p= 0.026). Smokers subjects under RAS blockade treatment exhibited higher percentage of ACE2-expressing type II pneumocytes than normotensive ones. Within the ACEI/ARB-treated group, the percentage of ACE2-expressing type II pneumocytes was higher in smokers than never smokers. A significant association between ACE2 immunostaining intensity and smoking on subjects over 60 years old was found (p= 0.05): older smokers exhibited higher ACE2 protein levels compared to youngers. The percentage of TMPRSS2-expressing type II pneumocytes was greater in men than women (p= 0.026) and in subjects under 60 years old (p= 0.040) and trend to be higher in ACEI/ARB-treated subjects than normotensives (p= 0.060). A significant association between TMPRSS2 immunostaining intensity with smoking and age or with RAS blockade and age or with RAS blockade and smoking was observed. Older or smokers subjects under ACEI/ARB treatment exhibited higher TMPRSS2 protein levels than youngers or never smokers.Conclusions—ACE2 and TMPRSS2 are influenced by smoking and ACEI/ARB treatment. These findings help explain the increased susceptibility to COVID-19 in subjects with treated cardiovascular-related pathologies.

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Cell differentiation and aging is accompanied by depletion of the ACE2 protein

Cited by 12 publications

References 18 publications

Expression of SARS-CoV-2 entry factors in lung epithelial stem cells and its potential implications for COVID-19

Expression of SARS-CoV-2 entry factors in lung epithelial stem cells and its potential implications for COVID-19

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Renin-Angiotensin System Blockade Influences ACE2 in Human Type II Pneumocytes

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