@article{409c0f506f4f4ad0abf5a2c8875974e1,
title = "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.",
keywords = "Adrenergic beta-Antagonists/pharmacology, Adult, Age Factors, Aged, Angiotensin Receptor Antagonists/pharmacology, Angiotensin-Converting Enzyme 2/genetics, 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, Kidney Tubules/metabolism, 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",
author = "Xiao Jiang and Eales, {James M} and David Scannali and Alicja Nazgiewicz and Priscilla Prestes and Michelle Maier and Matthew Denniff and Xiaoguang Xu and Sushant Saluja and Eddie Cano-Gamez and Wojciech Wystrychowski and Monika Szulinska and Andrzej Antczak and Sean Byars and Damian Skrypnik and Maciej Glyda and Robert Kr{\'o}l and Joanna Zywiec and Ewa Zukowska-Szczechowska and Burrell, {Louise M} and Woolf, {Adrian S} and Adam Greenstein and Pawel Bogdanski and Bernard Keavney and Morris, {Andrew P} and Anthony Heagerty and Bryan Williams and Harrap, {Stephen B} and Gosia Trynka and Samani, {Nilesh J} and Guzik, {Tomasz J} and Charchar, {Fadi J} and Maciej Tomaszewski",
note = "Funding Information: This work was supported by British Heart Foundation project grants [PG/17/35/33001 and PG/19/16/34270] and Kidney Research UK [grant RP_017_20180302] to M.T., British Heart Foundation Personal Chair [CH/13/2/30154] and Manchester Academic Health Science Centre: Tissue Bank Grant to BK, Medical University of Silesia [grants KNW-1- 152/N/7/K to J.Z. and KNW-1-171/N/6/K to W.W.]. F.C. and S.H. were supported by a National Health and Medical Research project grant [APP1104686]. T.J.G. was supported by the European Research Council [InflammaTENSION; ERC-CoG-726318], T.J.G. also acknowledges support from ERA-CVD [PLAQUEFIGHT/5/2018]. L.M.B. acknowledges support from National Health and Medical Research Council Program [Grant APP1055214] and Medical Research Future Fund [APP 1175865]. G.T. is supported by Open Targets and the Wellcome Trust [grant WT206194]. E.C.G. is supported by the Gates Cambridge Scholarship [OPP1144]. Access to TCGA kidneys and GTEx data has been granted by NIH [approvals 50804-2 and 50805-2]. The results published here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.We thank the Oxford Genomics Centre at the Wellcome Centre for Human Genetics funded by Wellcome Trust [grant reference 203141/Z/16/Z] for the generation and initial processing of sequencing data. Publisher Copyright: {\textcopyright} The Author(s) 2020. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2020",
month = oct,
day = "27",
doi = "10.1093/eurheartj/ehaa794",
language = "English",
volume = "41",
pages = "4580--4588",
journal = "European Heart Journal ",
issn = "1522-9645",
publisher = "Oxford University Press",
number = "48",
}
