Nets, pulmonary arterial hypertension, and thrombo-inflammation

Pulmonary arterial hypertension (PAH) is a progressive and fatal vascular disease in which high blood pressure in the pulmonary artery and remodeling of the pulmonary vasculature ensues. This disorder is characterized by the presence of thrombotic lesions, resulting from chronic platelet, coagulation factors, and endothelium activation, which translate into platelet aggregation, vasoconstriction, and medial thickening. Neutrophil extracellular traps (NETs), a network of chromatin and cytoplasmatic enzymes (myeloperoxidase and neutrophil elastase) forming after neutrophil programmed cell death, were described in multiple cardiovascular diseases as thrombotic mediators, by creating a scaffold or by surface receptor interaction. In this review, we analyze the possible involvement of NETs in PAH, to enlighten future studies to explore this hypothesis. NETs may have a determining role in pulmonary hypertension through activation of platelets and endothelial cells. Simultaneously, NETosis may be induced by endothelial signaling and/or cell-cell interaction between platelets and primed neutrophils, creating a positive feedback loop. Confirming its role in the pathophysiology and prognosis of PAH may represent a new opportunity to explore new therapeutic options. Key messages Thrombosis and innate immunity are relevant axes in PAH. Patients with PAH display elevated levels of NETs. NETs could activate platelets/endothelium with proliferative and thrombotic effects. Activated platelets and endothelium could contribute to NETosis. NETs could open new therapy research avenues.

Automated summary

This review analyzes the potential involvement of neutrophil extracellular traps (NETs) in pulmonary arterial hypertension (PAH), highlighting their role in platelet and endothelial cell activation. The formation of NETs may be induced by endothelial signaling and platelet-neutrophil interaction, creating a positive feedback loop. Confirming the role of NETs in PAH could open up new avenues for therapeutic research.