Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney
| Autor: | Maciej Tomaszewski, Louise M Burrell, Stephen Harrap, Damian Skrypnik, Eddie Cano-Gamez, Sean G. Byars, Adam Greenstein, Maciej Glyda, Anthony M. Heagerty, Michelle C. Maier, Priscilla R. Prestes, Andrzej Antczak, Fadi J. Charchar, Xiao Jiang, Joanna Zywiec, Andrew P. Morris, Matthew Denniff, Bernard Keavney, Gosia Trynka, David Scannali, Xiaoguang Xu, Paweł Bogdański, Adrian S. Woolf, Alicja Nazgiewicz, Ewa Zukowska-Szczechowska, Wojciech Wystrychowski, James Eales, Bryan Williams, Tomasz J. Guzik, Nilesh J. Samani, Robert Król, Sushant Saluja, Monika Szulińska |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
ACE2 Lung/metabolism 030204 cardiovascular system & hematology Kidney Renin-Angiotensin System 0302 clinical medicine Diuretics/pharmacology Antihypertensive treatment Rats Inbred SHR AcademicSubjects/MED00200 Estimated glomerular filtration rate 0303 health sciences Angiotensin Receptor Antagonists biology Hypertension/drug therapy Age Factors Antihypertensive Agents/pharmacology Middle Aged Angiotensin-Converting Enzyme 2/genetics medicine.anatomical_structure Transcriptome/drug effects Hypertension Angiotensin-converting enzyme 2 COVID-19/complications Female Angiotensin-Converting Enzyme 2 Cardiology and Cardiovascular Medicine hormones hormone substitutes and hormone antagonists Glomerular Filtration Rate Adult medicine.medical_specialty Renal function Angiotensin Receptor Antagonists/pharmacology Angiotensin-Converting Enzyme Inhibitors/pharmacology 03 medical and health sciences Sex Factors Clinical Research Internal medicine Renin–angiotensin system medicine Animals Humans 030304 developmental biology Aged Lung business.industry SARS-CoV-2 Sequence Analysis RNA Gene Expression Profiling COVID-19 Kidney Tubules/metabolism Angiotensin-converting enzyme Rats Endocrinology Blood pressure Renin-Angiotensin System/drug effects biology.protein Adrenergic beta-Antagonists/pharmacology Transcriptome business |
| Zdroj: | Jiang, X, Eales, J M, Scannali, D, Nazgiewicz, A, Prestes, P, Maier, M, Denniff, M, Xu, X, Saluja, S, Cano-Gamez, E, Wystrychowski, W, Szulinska, M, Antczak, A, Byars, S, Skrypnik, D, Glyda, M, Król, R, Zywiec, J, Zukowska-Szczechowska, E, Burrell, L M, Woolf, A S, Greenstein, A, Bogdanski, P, Keavney, B, Morris, A P, Heagerty, A, Williams, B, Harrap, S B, Trynka, G, Samani, N J, Guzik, T J, Charchar, F J & Tomaszewski, M 2020, ' Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney ', European Heart Journal, vol. 41, no. 48, pp. 4580-4588 . https://doi.org/10.1093/eurheartj/ehaa794 Eur Heart J European Heart Journal |
| Popis: | Aims Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)—the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. Methods and results We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. Conclusion Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection. Graphical Abstract Graphical Abstract |
| Databáze: | OpenAIRE |
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