A novel anticoagulant protein with antithrombotic properties from the mosquito Culex pipiens pallens

A newly discovered protein, named 'CPP protein', which possesses antithrombotic and anticoagulant properties, was purified from the salivary gland of the mosquito Culex pipiens pallens. CPP protein was found to have an estimated molecular mass of 21.7kDa, and to be active at 60°C, and pH 7.0. The anticoagulation activity of CPP protein was strongly inhibited by calcium ions. CPP protein inhibited fibrin clot formation and platelet activation, and it degraded blood clots. It also inhibited the enzymatic activities of activated factor X and thrombin. In addition, CPP protein prolonged the activated partial thromboplastin time and prothrombin time. CPP protein demonstrated antithrombotic effect in two mouse models, a thrombin-induced acute thromboembolism model, and an ex vivo coagulation model. CPP protein at a dose of 20mg/kg was devoid of hemorrhagic activity. These results suggest that CPP protein could have potential as a therapeutic agent for thrombosis, due to its antithrombotic properties and lack of hemorrhagic activity.