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.

严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 的致病性归因于其能够通过膜结合血管紧张素转换酶 2 (ACE2) 受体进入。因此，人们推测血管紧张素转换酶抑制剂（ACEI）或血管紧张素受体阻滞剂（ARB）治疗可能会调节 SARS-CoV-2 感染。在这项研究中，将人多能干细胞衍生的心肌细胞 (hPSC-CM) 和人内皮细胞 (hEC) 暴露于 SARS-CoV-2，发现参与免疫、病毒反应和心肌细胞/内皮结构的蛋白质编码基因存在显着差异。具体而言，在肿瘤坏死因子 (TNF)、干扰素 α/β 和丝裂原激活蛋白激酶 (MAPK) (hPSC-CM) 以及核因子 kappa-B (NF-κB) (hEC) 中发现了转录组变化信号通路。然而，用两种广泛使用的抗高血压药物氯沙坦和赖诺普利对 hPSC-CM 或 hEC 进行预处理，并不影响这两种细胞类型对 SARS-CoV-2 感染的易感性。这些发现证明了 SARS-CoV-2 对 hPSC-CM/hEC 的毒性作用，并且与新出现的多中心试验相结合，表明单独的抗高血压药物治疗并不能改变 SARS-CoV-2 感染。