Kidney and Lung ACE2 Expression after an ACE Inhibitor or an Ang II Receptor Blocker: Implications for COVID-19.
Reads0
Chats0
TLDR
In this article, the ACE2 protein abundance in kidney membranes was reduced to 42 % of wild type, p < 0 05 In ACE 8/8 mice that over-express cardiac ACE protein but has no kidney ACE expression, ACE2protein in kidney membrane was also decreased (38 % of the WT, p< 0 01) In kidney membranes from mice that received captopril or telmisartan for 2 weeks there was a reduction in ACE2 proteins to the level of 37%, p<0 01 and 76%, p <0 05 of that of vehicle control mice,Abstract:
Background: There have been concerns that ACE inhibitors and Ang II receptor blockers may cause an increase in full length (FL) membrane bound ACE2, the main receptor for SARs-CoV-2, that could enhance the risk and worsen the clinical course of COVID -19 Information on the impact of ACE deficiency and AT1 blockade on ACE2 expression at target sites is required to understand this issue Methods: Kidneys from two genetic models of kidney ACE ablation and mice treated with captopril or telmisartan were used to examine ACE2 in isolated kidney and lung membranes Results: In global ACE KO mice, ACE2 protein abundance in kidney membranes was reduced to 42 % of wild type, p < 0 05 In ACE 8/8 mice that over-express cardiac ACE protein but has no kidney ACE expression, ACE2 protein in kidney membranes wasalso decreased (38 % of the WT, p<0 01) In kidney membranes from mice that received captopril or telmisartan for 2 weeks there was a reduction in ACE2 protein to the level of 37%, p<0 01 and 76%, p <0 05 of that of vehicle control mice, respectively In lung membranes the expression of ACE2 was very low and not detected by western blotting but no significant differences in terms of ACE2 activity could be detected in mice treated with captopril (118% of control) or telmisartan (93% of control) Conclusions: Genetic kidney ACE deficiency, suppressed ACE enzyme activity by Captopril or blockade of the AT1 receptor with telmisartan are all associated with a decrease in ACE2 expression in kidney membranes These findings altogether suggest that ACE2 protein abundance at two potential target sites for SARS-CoV-2 infection is decreased or unaffected by RAS blockers Since these medications do not increase ACE2 expression in lung or kidney epithelia, we conclude that they likely would not pose a risk for increased susceptibility to COVID -19read more
Citations
More filters
Journal ArticleDOI
Pathophysiology of COVID-19-associated acute kidney injury.
Matthieu Legrand,Samira Bell,Lui G. Forni,Michael Joannidis,Jay L. Koyner,Kathleen D. Liu,Vincenzo Cantaluppi +6 more
TL;DR: A number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection are investigated in this article.
Journal ArticleDOI
Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.
Jordana B. Cohen,Thomas C. Hanff,Thomas C. Hanff,Preethi William,Nancy K. Sweitzer,Nelson R. Rosado-Santander,Carola Medina,Juan E. Rodriguez-Mori,Nicolas Federico Renna,Tara I. Chang,Vicente F. Corrales-Medina,Jaime Andrade-Villanueva,Alejandro Barbagelata,Roberto Cristodulo-Cortez,Omar A Díaz-Cucho,Jonas Spaak,Carlos Alfonso,Renzo P. Valdivia-Vega,Mirko Villavicencio-Carranza,Ricardo J Ayala-García,Carlos Augusto Castro-Callirgos,Luz A. González-Hernández,Eduardo F Bernales-Salas,Johanna C. Coacalla-Guerra,Cynthia D Salinas-Herrera,Liliana Nicolosi,Mauro Basconcel,James Brian Byrd,Tiffany Sharkoski,Luis E Bendezú-Huasasquiche,Jesse Chittams,Daniel L. Edmonston,Charles R. Vasquez,Charles R. Vasquez,Julio A. Chirinos +34 more
TL;DR: The REPLACE COVID trial as mentioned in this paper evaluated whether continuing versus discontinuing renin-angiotensin system inhibitors (ANGI-converting enzyme inhibitors or angiotENSin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.
Journal ArticleDOI
The emergence of COVID-19 as a global pandemic: Understanding the epidemiology, immune response and potential therapeutic targets of SARS-CoV-2.
TL;DR: The epidemiology, entry mechanism, immune response, and therapeutic implications, possible drug targets, their ongoing clinical trials, and vital questions are put forward to offer new directions to the COVID-19 research are summarized.
Journal ArticleDOI
Interaction of SARS-CoV-2 and Other Coronavirus With ACE (Angiotensin-Converting Enzyme)-2 as Their Main Receptor: Therapeutic Implications.
TL;DR: The current understanding of the interaction of SARS-CoV-2 with ACE2 is reviewed as it has rapidly unfolded over the last months with clear therapeutic implications.
Journal ArticleDOI
Metabolomics Profiling of Critically Ill Coronavirus Disease 2019 Patients: Identification of Diagnostic and Prognostic Biomarkers
Douglas D. Fraser,Marat Slessarev,Marat Slessarev,Claudio Martin,Claudio Martin,Mark Daley,Mark Daley,Maitray A. Patel,Michael R. Miller,Michael R. Miller,Eric K. Patterson,David B. O’Gorman,David B. O’Gorman,Sean E. Gill,Sean E. Gill,David S. Wishart,Rupasri Mandal,Gediminas Cepinskas,Gediminas Cepinskas +18 more
TL;DR: Metabolomics profiling of critically ill coronavirus disease 2019 patients to understand better the underlying pathologic processes and pathways, and to identify potential diagnostic/prognostic biomarkers.
References
More filters
Journal ArticleDOI
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann,Hannah Kleine-Weber,Simon Schroeder,Nadine Krüger,Tanja Herrler,Sandra Erichsen,Tobias S. Schiergens,Georg Herrler,Nai Huei Wu,Andreas Nitsche,Marcel A. Müller,Christian Drosten,Christian Drosten,Stefan Pöhlmann +13 more
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
Journal ArticleDOI
Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis
TL;DR: ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS‐CoV.
Journal ArticleDOI
Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?
TL;DR: It is suggested that patients with cardiac diseases, hypertension, or diabetes, who are treated with ACE2increasing drugs, are at higher risk for severe COVID-19 infection and, therefore, should be monitored for ACE2-modulating medications, such as ACE inhibitors or ARBs.
Journal ArticleDOI
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.
Carly G. K. Ziegler,Samuel J. Allon,Sarah K. Nyquist,Ian M. Mbano,Vincent N. Miao,Constantine N. Tzouanas,Yuming Cao,Ashraf S. Yousif,Julia Bals,Blake M. Hauser,Blake M. Hauser,Jared Feldman,Jared Feldman,Christoph Muus,Christoph Muus,Marc H. Wadsworth,Samuel W. Kazer,Travis K. Hughes,Benjamin Doran,G. James Gatter,G. James Gatter,G. James Gatter,Marko Vukovic,Faith Taliaferro,Faith Taliaferro,Benjamin E. Mead,Zhiru Guo,Jennifer P. Wang,Delphine Gras,Magali Plaisant,Meshal Ansari,Ilias Angelidis,Heiko Adler,Jennifer M.S. Sucre,Chase J. Taylor,Brian M. Lin,Avinash Waghray,Vanessa Mitsialis,Vanessa Mitsialis,Daniel F. Dwyer,Kathleen M. Buchheit,Joshua A. Boyce,Nora A. Barrett,Tanya M. Laidlaw,Shaina L. Carroll,Lucrezia Colonna,Victor Tkachev,Victor Tkachev,Christopher W. Peterson,Christopher W. Peterson,Alison Yu,Alison Yu,Hengqi Betty Zheng,Hengqi Betty Zheng,Hannah P. Gideon,Caylin G. Winchell,Philana Ling Lin,Philana Ling Lin,Colin D. Bingle,Scott B. Snapper,Scott B. Snapper,Jonathan A. Kropski,Jonathan A. Kropski,Fabian J. Theis,Herbert B. Schiller,Laure-Emmanuelle Zaragosi,Pascal Barbry,Alasdair Leslie,Alasdair Leslie,Hans-Peter Kiem,Hans-Peter Kiem,JoAnne L. Flynn,Sarah M. Fortune,Sarah M. Fortune,Sarah M. Fortune,Bonnie Berger,Robert W. Finberg,Leslie S. Kean,Leslie S. Kean,Manuel Garber,Aaron G. Schmidt,Aaron G. Schmidt,Daniel Lingwood,Alex K. Shalek,Jose Ordovas-Montanes,Nicholas E. Banovich,Alvis Brazma,Tushar J. Desai,Thu Elizabeth Duong,Oliver Eickelberg,Christine S. Falk,Michael Farzan,Ian A. Glass,Muzlifah Haniffa,Peter Horvath,Deborah T. Hung,Naftali Kaminski,Mark A. Krasnow,Malte Kühnemund,Robert Lafyatis,Haeock Lee,Sylvie Leroy,Sten Linnarson,Joakim Lundeberg,Kerstin B. Meyer,Alexander V. Misharin,Martijn C. Nawijn,Marko Nikolic,Dana Pe'er,Joseph E. Powell,Stephen R. Quake,Jay Rajagopal,Purushothama Rao Tata,Emma L. Rawlins,Aviv Regev,Paul A. Reyfman,Mauricio Rojas,Orit Rosen,Kourosh Saeb-Parsy,Christos Samakovlis,Herbert B. Schiller,Joachim L. Schultze,Max A. Seibold,Douglas P. Shepherd,Jason R. Spence,Avrum Spira,Xin Sun,Sarah A. Teichmann,Fabian J. Theis,Alexander M. Tsankov,Maarten van den Berge,Michael von Papen,Jeffrey A. Whitsett,Ramnik J. Xavier,Yan Xu,Kun Zhang +135 more
TL;DR: The data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.
Journal ArticleDOI
Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19.
Muthiah Vaduganathan,Orly Vardeny,Thomas Michel,John J.V. McMurray,Marc A. Pfeffer,Scott D. Solomon +5 more
TL;DR: RAAS Inhibitors in Patients with Covid-19 show low levels of renin–angiotensin-converting enzyme 2 levels and activity in humans, but the effects are still uncertain.