Neutrophil extracellular traps formation may be involved in the association of propranolol with the development of portal vein thrombosis.

Nonselective β blockers (NSBBs) facilitate the development of portal vein thrombosis (PVT) in liver cirrhosis. Considering the potential effect of NSBBs on neutrophils and neutrophil extracellular traps (NETs), we speculated that NSBBs might promote the development of PVT by stimulating neutrophils to release NETs. Serum NETs biomarkers were measured, use of NSBBs was recorded, and PVT was evaluated in cirrhotic patients. Carbon tetrachloride and ferric chloride (FeCl 3) were used to induce liver fibrosis and PVT in mice, respectively. After treatment with propranolol and DNase I, neutrophils in peripheral blood, colocalization and expression of NETs in PVT specimens, and NETs biomarkers in serum were measured. Ex vivo clots lysis analysis was performed and portal vein velocity and coagulation parameters were tested. Serum MPO-DNA level was significantly higher in cirrhotic patients treated with NSBBs, and serum H3Cit and MPO-DNA levels were significantly higher in those with PVT. In fibrotic mice, following treatment with propranolol, DNase I significantly shortened the time of FeCl 3 -induced PVT formation, lowered the peripheral blood neutrophils labelled by CD11b/Ly6G, inhibited the positive staining of H3Cit and the expression of H3Cit and MPO proteins in PVT tissues, and reduced serum nucleosome level. Furthermore, the addition of DNase I to tissue plasminogen activator (tPA) significantly accelerated clots lysis as compared with tPA alone. Propranolol reduced portal vein velocity in fibrotic mice, but did not influence coagulation parameters. Our study provides a clue to the potential impact of NETs formation on the association of NSBBs with the development of PVT. [Display omitted] • Nonselective β blockers (NSBBs) can increase the risk of portal vein thrombosis (PVT) in patients with liver cirrhosis. • NSBBs may influence neutrophil extracellular traps (NETs) formation, which can affect the development of thrombosis. • Clinical studies supported the association of serum NETs biomarkers with use of NSBBs and PVT in cirrhotic patients. • Experimental studies suggested that NETs formation may participate in the effect of NSBBs on the development of FeCl 3 -induced PVT model. [ABSTRACT FROM AUTHOR]