Prenylcysteine Oxidase 1 (PCYOX1), a New Player in Thrombosis.

Prenylcysteine Oxidase 1 (PCYOX1) is an enzyme involved in the degradation of prenylated proteins. It is expressed in different tissues including vascular and blood cells. We recently showed that the secretome from -silenced cells reduced platelet adhesion both to fibrinogen and endothelial cells, suggesting a potential contribution of PCYOX1 into thrombus formation. Here, we show that in vivo thrombus formation after FeCl injury of the carotid artery was delayed in Pcyox1 mice, which were also protected from collagen/epinephrine induced thromboembolism. The Pcyox1 mice displayed normal blood cells count, vascular procoagulant activity and plasma fibrinogen levels. Deletion of reduced the platelet/leukocyte aggregates in whole blood, as well as the platelet aggregation, the alpha granules release, and the αβ integrin activation in platelet-rich plasma, in response to adenosine diphosphate (ADP) or thrombin receptor agonist peptide (TRAP). Washed platelets from the Pcyox1 and WT animals showed similar phosphorylation pathway activation, adhesion ability and aggregation. The presence of Pcyox1 plasma impaired agonist-induced WT platelet aggregation. Our findings show that the absence of PCYOX1 results in platelet hypo-reactivity and impaired arterial thrombosis, and indicates that PCYOX1 could be a novel target for antithrombotic drugs.