Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney.

Abstract

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.

• Authors: Xiao Jiang, James M Eales, David Scannali, Alicja Nazgiewicz, Priscilla Prestes, Michelle Maier, Matthew Denniff, Xiaoguang Xu, Sushant Saluja, Eddie Cano-Gamez, Wojciech Wystrychowski, Monika Szulinska, Andrzej Antczak, Sean Byars, Damian Skrypnik, Maciej Glyda, Robert Król, Joanna Zywiec, Ewa Zukowska-Szczechowska, Louise M Burrell, Adrian S Woolf, Adam Greenstein, Pawel Bogdanski, Bernard Keavney, Andrew P Morris, Anthony Heagerty, Bryan Williams, Stephen B Harrap, Gosia Trynka, Nilesh J Samani, Tomasz J Guzik, Fadi J Charchar, Maciej Tomaszewski
• Journal: European heart journal (Eur Heart J) Vol. 41 Issue 48 Pg. 4580-4588 (12 21 2020) ISSN: 1522-9645 [Electronic] England
• PMID: 33206176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Chemical References

• Adrenergic beta-Antagonists
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Diuretics
• Angiotensin-Converting Enzyme 2

Topics

• Adrenergic beta-Antagonists (pharmacology)
• Adult
• Age Factors
• Aged
• Angiotensin Receptor Antagonists (pharmacology)
• Angiotensin-Converting Enzyme 2 (genetics, metabolism)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• COVID-19 (complications)
• Diuretics (pharmacology)
• Female
• Gene Expression Profiling
• Glomerular Filtration Rate
• Humans
• Hypertension (drug therapy, genetics)
• Kidney Tubules (metabolism, physiopathology)
• Lung (metabolism)
• Male
• Middle Aged
• Rats
• Rats, Inbred SHR
• Renin-Angiotensin System (drug effects)
• SARS-CoV-2
• Sequence Analysis, RNA
• Sex Factors
• Transcriptome (drug effects)