Shear Stress-Induced Activation of von Willebrand Factor and Cardiovascular Pathology

International Journal of Molecular Sciences

Ivan Melnikov¹  Yuliya Avtaeva¹  Sergey Okhota¹  Sergey Kozlov¹  Zufar Gabbasov¹ 

[1] National Medical Research Centre of Cardiology of the Ministry of Health of the Russian Federation, 15A, 3-rd Cherepkovskaya Street, 121552 Moscow, Russia;

关键词: von Willebrand factor;    ADAMTS-13;    atherosclerosis;    atherothrombosis;    coronary artery disease;    Heyde’s syndrome;   

DOI  :  10.3390/ijms21207804

来源: DOAJ

【 摘 要 】

The von Willebrand factor (vWF) is a plasma protein that mediates platelet adhesion and leukocyte recruitment to vascular injury sites and carries coagulation factor VIII, a building block of the intrinsic pathway of coagulation. The presence of ultra-large multimers of vWF in the bloodstream is associated with spontaneous thrombosis, whereas its deficiency leads to bleeding. 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 vWF hemostatic activity, but vWF activation, triggered by a rise in shear rates. vWF becomes highly reactive with platelets upon unfolding into a stretched conformation, at shear rates above the critical value (more than 5000 s⁻¹), which might occur at sites of arterial stenosis and injury. The activation of vWF and its counterbalance by ADAMTS-13, the vWF-cleaving protease, might contribute to complications of cardiovascular diseases. In this review, we discuss vWF involvement in complications of cardiovascular diseases and possible diagnostic and treatment approaches.

【 授权许可】

Unknown