Platelet Adhesion Mediated by von Willebrand Factor at High Shear Rates Is Associated with Premature Coronary Artery Disease

Author:

Okhota Sergey1ORCID,Kozlov Sergey1ORCID,Avtaeva Yuliya2ORCID,Melnikov Ivan23ORCID,Saburova Olga2,Guria Konstantin2ORCID,Matroze Evgeny24,Gabbasov Zufar2ORCID

Affiliation:

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, 121552 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, 121552 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, 123007 Moscow, Russia

4. Department of Innovative Pharmacy, Medical Devices and Biotechnology, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia

Abstract

This study investigated von Willebrand factor (VWF)-mediated platelet adhesion at high shear rates in patients with premature coronary artery disease (CAD). The study included 84 patients with stable premature CAD and 64 patients without CAD. Whole blood samples were perfused through a microfluidic cell over a collagen-coated surface at a shear rate of 1300 s−1. Measurements were performed before and after the inhibition of VWF-specific platelet GPIb receptors with an anti-GPIb monoclonal antibody (mAb). Platelet adhesion decreased by 77.0% (55.9; 84.7) in patients with premature CAD and by 29.6% (0.0; 59.7) in control patients after the inhibition of VWF–platelet interaction with anti-GPIb mAb (p < 0.001). After adjusting for traditional risk factors, the odds ratio for premature CAD per 1% decrease in GPIb-mediated platelet adhesion was 1.03 (95% CI, 1.02–1.05; p < 0.001). The optimal cut-off level value of GPIb-mediated platelet adhesion was 62.8%, with 70.2% sensitivity and 81.2% specificity for CAD. The plasma levels of VWF or antiplatelet therapy did not affect the GPIb-mediated component of platelet adhesion. Thus, the GPIb-mediated component of platelet adhesion was more pronounced in patients with premature CAD. This may indicate the possible role of excessive VWF–platelet interactions in the development of premature CAD.

Funder

Russian Science Foundation

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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