Endothelial cells, neutrophils and platelets: getting to the bottom of an inflammatory triangle

Severe fibrotic and thrombotic events permeate the healthcare system, causing suffering for millions of patients with inflammatory disorders. As late-state consequences of chronic inflammation, fibrosis and thrombosis are the culmination of pathological interactions of activated endothelium, neutrophils and platelets after vessel injury. Coupling of these three cell types ensures a pro-coagulant, cytokine-rich environment that promotes the capture, activation and proliferation of circulating immune cells and recruitment of key pro-fibrotic cell types such as myofibroblasts. As the first responders to sterile inflammatory injury, it is important to understand how endothelial cells, neutrophils and platelets help create this environment. There has been a growing interest in this intersection over the past decade that has helped shape the development of therapeutics to target these processes. Here, we review recent insights into how neutrophils, platelets and endothelial cells guide the development of pathological vessel repair that can also result in underlying tissue fibrosis. We further discuss recent efforts that have been made to translate this knowledge into therapeutics and provide perspective as to how a compound or combination therapeutics may be most efficacious when tackling fibrosis and thrombosis that is brought upon by chronic inflammation.