2025-07-29 北海道大学
本研究成果の概要図
<関連情報>
- https://www.hokudai.ac.jp/news/2025/07/post-1995.html
- https://www.hokudai.ac.jp/news/pdf/250729_pr2.pdf
- https://www.pnas.org/doi/10.1073/pnas.2502724122
BSG/VEGFR2経路によって制御される老化血管内皮細胞によるSARS-CoV-2取り込みと炎症応答 SARS-CoV-2 uptake and inflammatory response in senescent endothelial cells are regulated by the BSG/VEGFR2 pathway
Yuya Sakurai, Yoichiro Fujioka, Nako Maishi, +10 , and Kyoko Hida
Proceedings of the National Academy of Sciences Published:July 28, 2025
DOI:https://doi.org/10.1073/pnas.2502724122
Significance
Despite the established link between COVID-19 and vascular endothelial dysfunction, the underlying mechanisms remain poorly understood. Our study provides the direct evidence of angiotensin-convertingenzyme 2 (ACE2)-independent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) uptake in vascular endothelial cells (ECs), which is significantly enhanced in aging and triggers a proinflammatory response. We reveal a molecular pathway linking endothelial senescence to increased viral susceptibility and inflammatory pathology, explaining why aging is a major risk factor for severe COVID-19. These findings not only resolve a long-standing controversy regarding SARS-CoV-2 infection of ECs but also identify senescent ECs as a promising therapeutic target for mitigating severe COVID-19 complications.
Abstract
Aging is a risk factor for severe COVID-19, characterized by vascular endothelial dysfunction. Although possible susceptibility of vascular endothelial cells (ECs) to SARS-CoV-2 infection has been suggested, the details of entry into cells have not been clarified. Previously, we reported that in an aged mouse model of severe COVID-19, ECs show a massive viral uptake and inflammatory response. Here, we focused on the endocytic capacity of senescent ECs. We found that the senescent ECs showed high endocytic capacity and SARS-CoV-2 virus uptake. This triggers an nuclear factor-kappa B (NF-κB) pathway–mediated inflammatory response. Further, Basigin enhanced endocytosis in the senescent ECs by activating the intracellular vascular endothelial growth factor signaling. Thus, EC senescence is associated with enhanced SARS-CoV-2 endocytosis and subsequent vascular endothelial dysfunction. This could prove a potential target for treating severe COVID-19 in older adults.
