Impact of Salt Intake and RAAS blockade on lung SARS CoV-2 Host Factors

Introduction: The angiotensin-converting enzyme 2 (ACE2) as well as the transmembrane protease serine type 2 (TMPRSS2) have been found to play roles in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19). SARS-CoV-2 infec...

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Main Authors: Xiaoli Zhang, Liping Liu, Mohamed M.S. Gaballa, Ahmed A Hasan, Yingquan Xiong, Li Xie, Thomas Klein, Denis Delic, Burkhard Kleuser, Bernhard K. Krämer, Jian Li, Berthold Hocher
Format: Article
Language:English
Published: Karger Publishers 2022-07-01
Series:Kidney & Blood Pressure Research
Online Access:https://beta.karger.com/Article/FullText/525368
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author Xiaoli Zhang
Liping Liu
Mohamed M.S. Gaballa
Ahmed A Hasan
Yingquan Xiong
Li Xie
Thomas Klein
Denis Delic
Burkhard Kleuser
Bernhard K. Krämer
Jian Li
Berthold Hocher
author_facet Xiaoli Zhang
Liping Liu
Mohamed M.S. Gaballa
Ahmed A Hasan
Yingquan Xiong
Li Xie
Thomas Klein
Denis Delic
Burkhard Kleuser
Bernhard K. Krämer
Jian Li
Berthold Hocher
author_sort Xiaoli Zhang
collection DOAJ
description Introduction: The angiotensin-converting enzyme 2 (ACE2) as well as the transmembrane protease serine type 2 (TMPRSS2) have been found to play roles in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection risk and severity of COVID-19 might be indicated by the expression of ACE2 and TMPRSS2 in the lung. Methods: A high salt diet rat model and RAAS blockade were used to test whether these factors affect ACE2 and TMPRSS2 expression of the lung. A normal (0.3% NaCl), a medium (2% NaCl), or a high (8% NaCl) salt diet was fed to rats for 12 weeks, along with enalapril or telmisartan, before examining the lung for histopathological alteration. Using immunofluorescence and qRT-PCR, the localization as well as mRNA expression of ACE2 and TMPRSS2 were investigated. Results: The findings provide evidence that both TMPRSS2 and ACE2 are highly expressed in bronchial epithelial cells as well as ACE2 was also expressed in alveolar type2 (AT2) cells. High salt diet exposure in rats leads to elevated ACE2 expression on protein level. Treatment with RAAS blockers had no effect on lung tissue expression of ACE2 and TMPRSS2. Conclusions: These findings offer biological support regarding the safety of these drugs that are often prescribed to COVID-19 patients with cardiovascular co-morbidity. High salt intake on the other hand might adversely affect COVID-19 outcome. Our preclinical data should stimulate clinical studies addressing this point of concern.
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spelling doaj.art-a821c7266a894f01bf849f180a29b09d2022-12-22T04:02:49ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432022-07-0110.1159/000525368525368Impact of Salt Intake and RAAS blockade on lung SARS CoV-2 Host FactorsXiaoli ZhangLiping LiuMohamed M.S. Gaballahttps://orcid.org/0000-0003-2949-430XAhmed A HasanYingquan XiongLi Xiehttps://orcid.org/0000-0002-2339-4917Thomas KleinDenis DelicBurkhard KleuserBernhard K. Krämerhttps://orcid.org/0000-0002-1718-2918Jian LiBerthold Hocherhttps://orcid.org/0000-0001-8143-0579Introduction: The angiotensin-converting enzyme 2 (ACE2) as well as the transmembrane protease serine type 2 (TMPRSS2) have been found to play roles in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection risk and severity of COVID-19 might be indicated by the expression of ACE2 and TMPRSS2 in the lung. Methods: A high salt diet rat model and RAAS blockade were used to test whether these factors affect ACE2 and TMPRSS2 expression of the lung. A normal (0.3% NaCl), a medium (2% NaCl), or a high (8% NaCl) salt diet was fed to rats for 12 weeks, along with enalapril or telmisartan, before examining the lung for histopathological alteration. Using immunofluorescence and qRT-PCR, the localization as well as mRNA expression of ACE2 and TMPRSS2 were investigated. Results: The findings provide evidence that both TMPRSS2 and ACE2 are highly expressed in bronchial epithelial cells as well as ACE2 was also expressed in alveolar type2 (AT2) cells. High salt diet exposure in rats leads to elevated ACE2 expression on protein level. Treatment with RAAS blockers had no effect on lung tissue expression of ACE2 and TMPRSS2. Conclusions: These findings offer biological support regarding the safety of these drugs that are often prescribed to COVID-19 patients with cardiovascular co-morbidity. High salt intake on the other hand might adversely affect COVID-19 outcome. Our preclinical data should stimulate clinical studies addressing this point of concern.https://beta.karger.com/Article/FullText/525368
spellingShingle Xiaoli Zhang
Liping Liu
Mohamed M.S. Gaballa
Ahmed A Hasan
Yingquan Xiong
Li Xie
Thomas Klein
Denis Delic
Burkhard Kleuser
Bernhard K. Krämer
Jian Li
Berthold Hocher
Impact of Salt Intake and RAAS blockade on lung SARS CoV-2 Host Factors
Kidney & Blood Pressure Research
title Impact of Salt Intake and RAAS blockade on lung SARS CoV-2 Host Factors
title_full Impact of Salt Intake and RAAS blockade on lung SARS CoV-2 Host Factors
title_fullStr Impact of Salt Intake and RAAS blockade on lung SARS CoV-2 Host Factors
title_full_unstemmed Impact of Salt Intake and RAAS blockade on lung SARS CoV-2 Host Factors
title_short Impact of Salt Intake and RAAS blockade on lung SARS CoV-2 Host Factors
title_sort impact of salt intake and raas blockade on lung sars cov 2 host factors
url https://beta.karger.com/Article/FullText/525368
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