Velefibrinase: A Marine-Derived Fibrinolytic Enzyme with Multi-Target Antithrombotic Effects Across Diverse In Vivo Models

<b>Background/Objectives:</b> Thrombotic diseases (TDs), currently the number one killer worldwide, account for the highest mortality rate globally. In this study, we evaluated the antithrombotic efficacy of Velefibrinase, a marine bacteria-derived fibrinolytic enzyme, across multiple animal models. <b>Results:</b> The results demonstrated that Velefibrinase prolonged bleeding time (BT) and clotting time (CT), reduced mortality and thrombosis, relieved pulmonary alveolar structure degeneration in an acute pulmonary thromboembolism model, and inhibited carotid artery thrombosis and endothelial tissue damage in a rat model of FeCl₃-induced carotid arterial thrombosis. Moreover, Velefibrinase reduced cerebral ischemia volume and ameliorated neurological deficits in a cerebral ischemia/reperfusion (I/R) injury model in rats. The putative underlying mechanisms were found to involve the inhibition of platelet aggregation and coagulation, along with the modulation of oxidative stress and inflammation levels. <b>Conclusions:</b> These results revealed that Velefibrinase exerts a notable thrombosis-preventive effect by interacting with multiple targets, thereby breaking the vicious cycle involving inflammation, oxidative stress, and thrombosis.