Journal of thrombosis and haemostasis : JTH · 2026
Shear cytokine crosstalk is a determinant of SARS-CoV-2-induced endothelial pathophysiology and thrombosis in human vessel chips.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Suresh Sreelakshmy, John Rebecca, Cooke John P, Connor John H, Jain Abhishek
Аннотация
BACKGROUND: SARS-CoV-2 infection is associated with systemic vasculopathy and thromboinflammation. However, the interaction between shear-dependent endothelial function, inflammatory signaling, and thrombosis during viral exposure remains incompletely defined due to limitations of conventional in vitro and animal models.
OBJECTIVES: To determine how flow modulates endothelial structure, barrier integrity, inflammatory activation, and thrombogenic responses during exposure to SARS-CoV-2 spike protein or the complete virus, with or without interleukin-6 (IL-6).
METHODS: A human endothelialized vessel chip platform was used to independently control flow (10 dyne/cm2) and IL-6 (100 pg/mL). Human endothelial cells (aortic, venous, and lymphatic) were exposed to vesicular stomatitis virus-ΔG-Spike and complete SARS-CoV-2 under static or flow conditions, with or without IL-6. Endpoints included cell morphology, junctional organization, permeability, viral replication, intercellular adhesion molecule 1 expression, and thrombotic markers.
RESULTS: Under static conditions, spike exposure disrupted endothelial morphology, disorganized intercellular junctions, and increased permeability. Flow mitigated these changes, preserving junctional organization and reducing barrier disruption during viral exposure. IL-6 induced cytoskeletal remodeling and barrier dysfunction, consistent with inflammatory activation. When shear stress, IL-6, and spike exposure were combined, flow preserved junctional architecture and reduced morphological injury, although IL-6-associated cytoskeletal alterations persisted. Flow reduced viral replication, permeability, and thrombotic markers by 40% to 60% compared with static or inflammatory conditions, whereas IL-6 increased these measures. vesicular stomatitis virus-ΔG-Spike and authentic SARS-CoV-2 produced concordant phenotypes across junctional metrics, intercellular adhesion molecule 1 induction, and replication.
CONCLUSION: Flow partially preserves endothelial homeostasis during viral and inflammatory challenges, limiting structural injury, viral replication, and thromboinflammatory activation. These findings highlight the vessel chip as a rigorous platform for dissecting flow-dependent vascular pathology.
OBJECTIVES: To determine how flow modulates endothelial structure, barrier integrity, inflammatory activation, and thrombogenic responses during exposure to SARS-CoV-2 spike protein or the complete virus, with or without interleukin-6 (IL-6).
METHODS: A human endothelialized vessel chip platform was used to independently control flow (10 dyne/cm2) and IL-6 (100 pg/mL). Human endothelial cells (aortic, venous, and lymphatic) were exposed to vesicular stomatitis virus-ΔG-Spike and complete SARS-CoV-2 under static or flow conditions, with or without IL-6. Endpoints included cell morphology, junctional organization, permeability, viral replication, intercellular adhesion molecule 1 expression, and thrombotic markers.
RESULTS: Under static conditions, spike exposure disrupted endothelial morphology, disorganized intercellular junctions, and increased permeability. Flow mitigated these changes, preserving junctional organization and reducing barrier disruption during viral exposure. IL-6 induced cytoskeletal remodeling and barrier dysfunction, consistent with inflammatory activation. When shear stress, IL-6, and spike exposure were combined, flow preserved junctional architecture and reduced morphological injury, although IL-6-associated cytoskeletal alterations persisted. Flow reduced viral replication, permeability, and thrombotic markers by 40% to 60% compared with static or inflammatory conditions, whereas IL-6 increased these measures. vesicular stomatitis virus-ΔG-Spike and authentic SARS-CoV-2 produced concordant phenotypes across junctional metrics, intercellular adhesion molecule 1 induction, and replication.
CONCLUSION: Flow partially preserves endothelial homeostasis during viral and inflammatory challenges, limiting structural injury, viral replication, and thromboinflammatory activation. These findings highlight the vessel chip as a rigorous platform for dissecting flow-dependent vascular pathology.