SARS-CoV-2 infection promotes lung thrombosis by inducing integrinβ3 expression in vascular endothelial cells

Area of Science:

• Cardiovascular Biology
• Immunology
• Respiratory Medicine

Background:

• Severe COVID-19 frequently causes pulmonary thrombosis, but the underlying molecular mechanisms are not fully understood.
• Endothelial cells (ECs) play a critical role in vascular homeostasis and thrombosis.

Purpose of the Study:

• To investigate the molecular mechanisms of pulmonary thrombosis in severe COVID-19.
• To identify specific molecular players involved in EC dysfunction and thrombosis.

Main Methods:

• RNA sequencing of endothelial cells from young and mid-aged infected mice.
• In vitro experiments assessing platelet adhesion to ECs.
• Knockdown of Integrinβ3 (ITGB3) in ECs.
• Histological analysis of mouse and human lung tissues.

Main Results:

• Mid-aged mice with lung thrombosis showed higher ITGB3 expression in ECs compared to young mice.
• SARS-CoV-2 exposure increased platelet adhesion to ECs, an effect reduced by ITGB3 knockdown.
• Kringle-containing transmembrane protein 1 was identified as a mediator of SARS-CoV-2-induced ITGB3 upregulation.
• ITGB3-positive blood vessels were prevalent in infected mouse lungs and COVID-19 human autopsy lungs.

Conclusions:

• Upregulation of ITGB3 in endothelial cells is a key mechanism contributing to thrombosis in severe COVID-19 pneumonia.
• ITGB3 plays a significant role in SARS-CoV-2-induced platelet adhesion and subsequent thrombosis.
• Targeting ITGB3 may offer a therapeutic strategy for preventing COVID-19-associated thrombosis.