Antihypertensive drug treatment and susceptibility to SARS-CoV-2 infection in human PSC-derived cardiomyocytes and primary endothelial cells.
Antihypertensive Agents
/ pharmacology
COVID-19
/ genetics
Cells, Cultured
Disease Susceptibility
Endothelial Cells
/ drug effects
Host-Pathogen Interactions
/ drug effects
Humans
Lisinopril
/ pharmacology
Losartan
/ pharmacology
Myocytes, Cardiac
/ drug effects
SARS-CoV-2
/ drug effects
Transcriptome
/ drug effects
COVID-19 Drug Treatment
COVID-19
Lisinopril
RNA sequencing
SARS-CoV-2
antihypertensive medication
endothelial cells
hPSC-derived cardiomyocytes
heart
losartan
stem cells
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
12 10 2021
12 10 2021
Historique:
received:
24
01
2021
revised:
29
08
2021
accepted:
30
08
2021
pubmed:
16
9
2021
medline:
27
10
2021
entrez:
15
9
2021
Statut:
ppublish
Résumé
The pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been attributed to its ability to enter through the membrane-bound angiotensin-converting enzyme 2 (ACE2) receptor. Therefore, it has been heavily speculated that angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy may modulate SARS-CoV-2 infection. In this study, exposure of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and human endothelial cells (hECs) to SARS-CoV-2 identified significant differences in protein coding genes involved in immunity, viral response, and cardiomyocyte/endothelial structure. Specifically, transcriptome changes were identified in the tumor necrosis factor (TNF), interferon α/β, and mitogen-activated protein kinase (MAPK) (hPSC-CMs) as well as nuclear factor kappa-B (NF-κB) (hECs) signaling pathways. However, pre-treatment of hPSC-CMs or hECs with two widely prescribed antihypertensive medications, losartan and lisinopril, did not affect the susceptibility of either cell type to SARS-CoV-2 infection. These findings demonstrate the toxic effects of SARS-CoV-2 in hPSC-CMs/hECs and, taken together with newly emerging multicenter trials, suggest that antihypertensive drug treatment alone does not alter SARS-CoV-2 infection.
Identifiants
pubmed: 34525378
pii: S2213-6711(21)00436-7
doi: 10.1016/j.stemcr.2021.08.018
pmc: PMC8407952
pii:
doi:
Substances chimiques
Antihypertensive Agents
0
Lisinopril
E7199S1YWR
Losartan
JMS50MPO89
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2459-2472Subventions
Organisme : NHLBI NIH HHS
ID : F30 HL151139
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL128906
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL123078
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007249
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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