Abstract
AimsAngiotensin-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 resultsWe 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.ConclusionOur 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.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19)—the recent viral pandemic with high mortality rates and overwhelming burden on the healthcare systems globally
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 angiotensin-converting enzyme 2 (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
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19)—the recent viral pandemic with high mortality rates and overwhelming burden on the healthcare systems globally. Whilst some have hypothesized that RAS blockers enhance SARSCoV-2 entry into the host cells[7,8] and/or promote the organ damage in patients with COVID-19 as a result of ACE2 up-regulation, there is evidence that RAS blockers have no influence on tissue or plasma ACE2 in animal models[9,10] or on plasma ACE2 activity in patients.[11,12] evidence for a direct effect of hypertension or RAS blockers on ACE2 expression in human tissues has remained elusive, largely because of the paucity of large gene expression datasets with matching clinical information. As the inhibition of the ACE2SARS-CoV-2 interaction gains traction as a potential treatment strategy for COVID-19,13 an urgent understanding of how the key COVID-19 comorbidities alter ACE2 expression in human tissues is necessary to gain new mechanistic and therapeutic insights
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