Antihypertensive drug treatment and susceptibility to SARS-CoV-2 infection in human PSC-derived cardiomyocytes and primary endothelial cells

Jessika Iwanski, Sobhi G. Kazmouz, Shuaizhi Li, Ben Stansfield, Tori T. Salem, Samantha Perez-Miller, Toshinobu Kazui, Lipsa Jena, Jennifer L. Uhrlaub, Scott Lick, Janko Nikolich-Žugich, John P. Konhilas, Carol C. Gregorio, May Khanna, Samuel K. Campos, Jared M. Churko

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2459-2472
Number of pages14
JournalStem Cell Reports
Volume16
Issue number10
DOIs
StatePublished - Oct 12 2021

Keywords

  • COVID-19
  • Lisinopril
  • RNA sequencing
  • SARS-CoV-2
  • antihypertensive medication
  • endothelial cells
  • hPSC-derived cardiomyocytes
  • heart
  • losartan
  • stem cells

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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