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.
【저자키워드】 COVID-19, stem cells, SARS-CoV-2, heart, endothelial cells, RNA sequencing, Lisinopril, antihypertensive medication, hPSC-derived cardiomyocytes, losartan, 【초록키워드】 Treatment, Transcriptome, stem cells, Necrosis, Tumor, ACE2, therapy, Immunity, SARS-COV-2 infection, susceptibility, interferon, severe acute respiratory syndrome coronavirus-2, medications, severe acute respiratory syndrome Coronavirus, angiotensin-converting enzyme 2, RNA, ARB, Severe acute respiratory syndrome, Protein, tumor necrosis factor, heart, endothelial cells, RNA sequencing, receptor, drug treatment, pathogenicity, signaling pathways, NF-κB, ACEi, Coronavirus-2, TNF, Endothelial cell, angiotensin receptor blocker, angiotensin-converting enzyme inhibitor, angiotensin, Lisinopril, antihypertensive medication, losartan, MAPK, Pathways, protein kinase, cell type, mitogen-activated protein kinase, toxic effects, tumor necrosis, receptor blocker, Antihypertensive drug, endothelial, acute respiratory syndrome, toxic effect, significant difference, acute respiratory syndrome coronavirus, significant differences, acute respiratory syndrome coronavirus-2, protein coding genes, mitogen, nuclear, Enzyme inhibitor, transcriptome changes, membrane-bound, Alter, Cell, involved, modulate, not affect, protein coding gene, multicenter trials, transcriptome change, 【제목키워드】 Treatment, susceptibility, Endothelial cell,