Von Willebrand factor in diagnostics and treatment of cardiovascular disease: Recent advances and prospects

Sergey Kozlov; Sergey Okhota; Yuliya Avtaeva; Ivan Melnikov; Evgeny Matroze; Zufar Gabbasov

doi:10.3389/fcvm.2022.1038030

Von Willebrand factor in diagnostics and treatment of cardiovascular disease: Recent advances and prospects

Front Cardiovasc Med. 2022 Dec 2:9:1038030. doi: 10.3389/fcvm.2022.1038030. eCollection 2022.

Authors

Sergey Kozlov¹, Sergey Okhota¹, Yuliya Avtaeva², Ivan Melnikov^{2

3}, Evgeny Matroze^{2

4}, Zufar Gabbasov²

Affiliations

¹ Department of Problems of Atherosclerosis, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Moscow, Russia.
² Laboratory of Cell Hemostasis, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Moscow, Russia.
³ Laboratory of Gas Exchange, Biomechanics and Barophysiology, State Scientific Center of the Russian Federation-The Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia.
⁴ Department of Innovative Pharmacy, Medical Devices and Biotechnology, Moscow Institute of Physics and Technology, Moscow, Russia.

Abstract

Von Willebrand factor (VWF) is a large multimeric glycoprotein involved in hemostasis. It is essential for platelet adhesion to the subendothelium of the damaged endothelial layer at high shear rates. Such shear rates occur in small-diameter arteries, especially at stenotic sites. Moreover, VWF carries coagulation factor VIII and protects it from proteolysis in the bloodstream. Deficiency or dysfunction of VWF predisposes to bleeding. In contrast, an increase in the concentration of high molecular weight multimers (HMWM) of VWF is closely associated with arterial thrombotic events. Severe aortic stenosis (AS) or hypertrophic obstructive cardiomyopathy (HOCM) can deplete HMWM of VWF and lead to cryptogenic, gastrointestinal, subcutaneous, and mucosal bleeding. Considering that VWF facilitates primary hemostasis and a local inflammatory response at high shear rates, its dysfunction may contribute to the development of coronary artery disease (CAD) and its complications. However, current diagnostic methods do not allow for an in-depth analysis of this contribution. The development of novel diagnostic techniques, primarily microfluidic, is underway. Such methods can provide physiologically relevant assessments of VWF function at high shear rates; however, they have not been introduced into clinical practice. The development and use of agents targeting VWF interaction with the vessel wall and/or platelets may be reasonable in prevention of CAD and its complications, given the prominent role of VWF in arterial thrombosis.

Keywords: ADAMTS-13; Heyde syndrome; cardiovascular disease; coronary artery disease; von Willebrand factor.

Publication types

Review