tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Sobhi G Kazmouz[SUP] 1 [/SUP], Shuaizhi Li[SUP] 2 [/SUP], Ben Stansfield[SUP] 3 [/SUP], Tori T Salem[SUP] 3 [/SUP], Samantha Perez-Miller[SUP] 4 [/SUP], Toshinobu Kazui[SUP] 5 [/SUP], Lipsa Jena[SUP] 4 [/SUP], Jennifer L Uhrlaub[SUP] 2 [/SUP], Scott Lick[SUP] 5 [/SUP], Janko Nikolich-Žugich[SUP] 6 [/SUP], John P Konhilas[SUP] 7 [/SUP], Carol C Gregorio[SUP] 1 [/SUP], May Khanna[SUP] 4 [/SUP], Samuel K Campos[SUP] 8 [/SUP], Jared M Churko[SUP] 9 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Sobhi G Kazmouz[SUP] 1 [/SUP], Shuaizhi Li[SUP] 2 [/SUP], Ben Stansfield[SUP] 3 [/SUP], Tori T Salem[SUP] 3 [/SUP], Samantha Perez-Miller[SUP] 4 [/SUP], Toshinobu Kazui[SUP] 5 [/SUP], Lipsa Jena[SUP] 4 [/SUP], Jennifer L Uhrlaub[SUP] 2 [/SUP], Scott Lick[SUP] 5 [/SUP], Janko Nikolich-Žugich[SUP] 6 [/SUP], John P Konhilas[SUP] 7 [/SUP], Carol C Gregorio[SUP] 1 [/SUP], May Khanna[SUP] 4 [/SUP], Samuel K Campos[SUP] 8 [/SUP], Jared M Churko[SUP] 9 [/SUP]
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.