Abstract
Thromboinflammation, the interplay between thrombosis and inflammation, is a significant pathway that drives cardiovascular and autoimmune diseases, as well as COVID-19. SARS-CoV-2 causes inflammation and blood clotting issues. Innate immune cells have emerged as key modulators of this process. Neutrophils, the most predominant white blood cells in humans, are strategically positioned to promote thromboinflammation. By releasing decondensed chromatin structures called neutrophil extracellular traps (NETs), neutrophils can initiate an organised cell death pathway. These structures are adorned with histones, cytoplasmic and granular proteins, and have cytotoxic, immunogenic, and prothrombotic effects that can hasten disease progression. Protein arginine deiminase 4 (PAD4) catalyses the citrullination of histones and is involved in the release of extracellular DNA (NETosis). The neutrophil inflammasome is also required for this process. Understanding the link between the immunological function of neutrophils and the procoagulant and proinflammatory activities of monocytes and platelets is important in understanding thromboinflammation. This text discusses how vascular blockages occur in thromboinflammation due to the interaction between neutrophil extracellular traps and ultra-large VWF (von Willebrand Factor). The activity of PAD4 is important for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. This article reviews how vaso-occlusive events in thrombo-inflammation occur through the interaction of neutrophil extracellular traps with von Willebrand factor. It highlights the relevance of PAD4 in neutrophil inflammasome assembly and neutrophil extracellular traps in thrombo-inflammatory diseases such as atherosclerosis and cardiovascular disease. Interaction between platelets, VWF, NETs and inflammasomes is critical for the progression of thromboinflammation in several diseases and was recently shown to be active in COVID-19.