Journal
STEM CELL REPORTS
Volume 16, Issue 10, Pages 2459-2472Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2021.08.018
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Funding
- Sarver Heart Center Investigator Awards
- National Heart, Lung, and Blood Institute of the National Institutes of Health [R00HL128906, F30HL151139, T32HL007249]
- Steven M. Gootter Foundation
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This study observed significant differences in protein coding genes related to immunity, viral response, and cell structure in human pluripotent stem cell-derived cardiomyocytes and human endothelial cells exposed to SARS-CoV-2. However, pre-treatment with two commonly used antihypertensive medications did not alter the susceptibility of these cells to SARS-CoV-2 infection. These findings suggest that antihypertensive drug treatment alone may not impact SARS-CoV-2 infection.
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 a/b, and mitogen-activated protein kinase (MAPK) (hPSC-CMs) as well as nuclear factor kappa-B (NF-kB) (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.
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