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Stem Cell Reports ; 16(10): 2459-2472, 2021 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-34525378

RESUMEN

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/ß, 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.


Asunto(s)
Antihipertensivos/farmacología , Tratamiento Farmacológico de COVID-19 , Células Endoteliales/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , COVID-19/genética , Células Cultivadas , Susceptibilidad a Enfermedades , Células Endoteliales/metabolismo , Interacciones Huésped-Patógeno/efectos de los fármacos , Humanos , Lisinopril/farmacología , Losartán/farmacología , Miocitos Cardíacos/metabolismo , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/fisiología , Transcriptoma/efectos de los fármacos
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