Tweet
Stem Cell Reports
. 2021 Sep 1;S2213-6711(21)00436-7.
doi: 10.1016/j.stemcr.2021.08.018. Online ahead of print.
Antihypertensive drug treatment and susceptibility to SARS-CoV-2 infection in human PSC-derived cardiomyocytes and primary endothelial cells
Jessika Iwanski 1 , Sobhi G Kazmouz 1 , Shuaizhi Li 2 , Ben Stansfield 3 , Tori T Salem 3 , Samantha Perez-Miller 4 , Toshinobu Kazui 5 , Lipsa Jena 4 , Jennifer L Uhrlaub 2 , Scott Lick 5 , Janko Nikolich-Žugich 6 , John P Konhilas 7 , Carol C Gregorio 1 , May Khanna 4 , Samuel K Campos 8 , Jared M Churko 9
Affiliations
- PMID: 34525378
- DOI: 10.1016/j.stemcr.2021.08.018
Abstract
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.
Keywords: COVID-19; Lisinopril; RNA sequencing; SARS-CoV-2; antihypertensive medication; endothelial cells; hPSC-derived cardiomyocytes; heart; losartan; stem cells.