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Thromboinflammation: From Atherosclerosis to COVID-19
Denisa D Wagner1, Lukas A Heger1
1Program in Cellular and Molecular Medicine, Division of Hematology and Oncology, Boston Children's Hospital/Harvard Medical School, MA (D.D.W., L.A.H.).
Arteriosclerosis, Thrombosis, and Vascular Biology
|July 21, 2022
Summary
Protein arginine deiminase 4 (PAD4) drives thromboinflammation by linking neutrophil extracellular traps (NETs) to thrombosis and inflammation. PAD4 activity is crucial in diseases like atherosclerosis and COVID-19.
Area of Science:
- Immunology
- Vascular Biology
- Pathophysiology
Background:
- Thromboinflammation, the interplay of thrombosis and inflammation, underlies cardiovascular, autoimmune, and infectious diseases like COVID-19.
- Innate immune cells, particularly neutrophils, are key modulators of thromboinflammation.
- Neutrophils release neutrophil extracellular traps (NETs), which promote thrombosis and inflammation.
Purpose of the Study:
- To explore the role of protein arginine deiminase 4 (PAD4) in neutrophil-mediated thromboinflammation.
- To elucidate the mechanisms by which PAD4 contributes to vascular occlusion and disease progression.
- To discuss the implications of PAD4 activity in thromboinflammatory diseases.
Main Methods:
- Investigated the role of PAD4 in NETosis (neutrophil extracellular trap release).
- Examined the interaction of NETs with von Willebrand Factor (VWF).
- Discussed the link between PAD4, neutrophil inflammasome, and NET formation.
Main Results:
- PAD4 activity is essential for NETosis and histone citrullination.
- NETs, decorated with proteins, exhibit cytotoxic, immunogenic, and prothrombotic effects.
- PAD4 links neutrophil functions to monocyte and platelet procoagulant activities.
Conclusions:
- PAD4 plays a critical role in driving thromboinflammation.
- Understanding PAD4's function in NET formation is vital for targeting diseases like atherosclerosis and COVID-19.
- NETs, mediated by PAD4, are crucial in vascular occlusion within thromboinflammation.
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