tetano
Editor, Senior Moderator
Sci Rep
. 2022 Jul 25;12(1):11855.
doi: 10.1038/s41598-022-15976-z.
Senescent endothelial cells are predisposed to SARS-CoV-2 infection and subsequent endothelial dysfunction
Ryota Urata[SUP] 1 [/SUP], Koji Ikeda[SUP] 2 3 [/SUP], Ekura Yamazaki[SUP] 1 [/SUP], Daisuke Ueno[SUP] 1 [/SUP], Akiko Katayama[SUP] 1 [/SUP], Masaharu Shin-Ya[SUP] 4 [/SUP], Eriko Ohgitani[SUP] 4 [/SUP], Osam Mazda[SUP] 4 [/SUP], Satoaki Matoba[SUP] 1 [/SUP]
Affiliations
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.
. 2022 Jul 25;12(1):11855.
doi: 10.1038/s41598-022-15976-z.
Senescent endothelial cells are predisposed to SARS-CoV-2 infection and subsequent endothelial dysfunction
Ryota Urata[SUP] 1 [/SUP], Koji Ikeda[SUP] 2 3 [/SUP], Ekura Yamazaki[SUP] 1 [/SUP], Daisuke Ueno[SUP] 1 [/SUP], Akiko Katayama[SUP] 1 [/SUP], Masaharu Shin-Ya[SUP] 4 [/SUP], Eriko Ohgitani[SUP] 4 [/SUP], Osam Mazda[SUP] 4 [/SUP], Satoaki Matoba[SUP] 1 [/SUP]
Affiliations
- PMID: 35879338
- DOI: 10.1038/s41598-022-15976-z
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.