Von Willebrand Factor in Thrombo-inflammation and Cardiovascular Pathology

Abstract

Von Willebrand factor (VWF) is a large multimeric plasma glycoprotein that links thrombosis and inflammation. It mediates platelet adhesion and leukocyte recruitment to vascular injury sites and carries coagulation factor VIII, a building block of the intrinsic pathway of coagulation. VWF may serve as a bridge between bacteria and the vessel wall in sepsis. The presence of ultra-large multimers of VWF in the bloodstream is associated with spontaneous thrombosis, whereas its deficiency leads to bleeding. Deficiency of VWF multimers also causes disturbances in angiogenesis and predisposes to the development of angiodysplasia. In cardiovascular pathology, the progression of the heart valve disease results in VWF deficiency and cryptogenic gastrointestinal bleeding. The association between higher plasma levels of VWF and thrombotic complications of coronary artery disease was described. Of note, it is not the plasma levels that are crucial for hemostatic and proinflammatory activity of VWF, but VWF activation, triggered by a rise in shear rates. VWF becomes highly reactive with platelets and leukocytes upon unfolding into a stretched conformation, at shear rates above the critical value (more than 5000 s^-1), which occur at sites of arterial stenosis and injury. The activation of VWF and its counterbalance by ADAMTS-13, the VWF-cleaving protease, may contribute to complications of cardiovascular diseases. In this review, we discuss the involvement of VWF in thrombo-inflammatory complications of cardiovascular diseases and possible diagnostic and treatment approaches.