Abstract
The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains to spread worldwide. COVID-19 is characterized by the striking high mortality in elderly; however, its mechanistic insights remain unclear. Systemic thrombosis has been highlighted in the pathogenesis of COVID-19, and lung microangiopathy in association with endothelial cells (ECs) injury has been reported by post-mortem analysis of the lungs. Here, we experimentally investigated the SARS-CoV-2 infection in cultured human ECs, and performed a comparative analysis for post-infection molecular events using early passage and replicative senescent ECs. We found that; (1) SARS-CoV-2 infects ECs but does not replicate and disappears in 72 hours without causing severe cell damage, (2) Senescent ECs are highly susceptible to SARS-CoV-2 infection, (3) SARS-CoV-2 infection alters various genes expression, which could cause EC dysfunctions, (4) More genes expression is affected in senescent ECs by SARS-CoV-2 infection than in early passage ECs, which might causes further exacerbated dysfunction in senescent ECs. These data suggest that sustained EC dysfunctions due to SARS-CoV-2 infection may contribute to the microangiopathy in the lungs, leading to deteriorated inflammation and thrombosis in COVID-19. Our data also suggest a possible causative role of EC senescence in the aggravated disease in elder COVID-19 patients.
【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, Inflammation, coronavirus, thrombosis, SARS-COV-2 infection, Infection, lung, Spread, Lungs, Post-mortem, molecular, disease, expression, COVID-19 patients, association, Endothelial cell, Analysis, Injury, systemic, dysfunction, Post-infection, acute respiratory syndrome, high mortality, pathogenesis of COVID-19, cell damage, infect, Alter, susceptible, event, performed, affected, caused, reported, investigated, exacerbated, replicate, characterized, contribute, cause, senescent, sustained, replicative, the SARS-CoV-2, 【제목키워드】 SARS-COV-2 infection, Endothelial dysfunction, Endothelial cell, subsequent,