Thromb Haemost 2022; 122(06): 974-983
DOI: 10.1055/a-1677-9499
Cellular Haemostasis and Platelets

Important Regulatory Roles of Erythrocytes in Platelet Adhesion to the von Willebrand Factor on the Wall under Blood Flow Conditions

Noriko Tamura
1   Department of Medicine (Cardiology), Research Center for Metabolic Disease, Tokai University School of Medicine and Tokai University Graduate School of Medicine, Isehara, Japan
2   Department of Health and Nutrition, Niigata University of Health and Welfare, Niigata, Japan
,
Kazuya Shimizu
3   Department of Bio-engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan
,
Seiji Shiozaki
3   Department of Bio-engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan
,
Kazuyasu Sugiyama
4   Department of Mechanical Science and Bioengineering, Osaka University School of Engineering Science, Osaka, Japan
,
Masamitsu Nakayama
1   Department of Medicine (Cardiology), Research Center for Metabolic Disease, Tokai University School of Medicine and Tokai University Graduate School of Medicine, Isehara, Japan
,
Shinichi Goto
1   Department of Medicine (Cardiology), Research Center for Metabolic Disease, Tokai University School of Medicine and Tokai University Graduate School of Medicine, Isehara, Japan
,
Shu Takagi
3   Department of Bio-engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan
,
1   Department of Medicine (Cardiology), Research Center for Metabolic Disease, Tokai University School of Medicine and Tokai University Graduate School of Medicine, Isehara, Japan
› Author Affiliations
Funding We acknowledge the support of the Strategic Program for Innovational Research Field 1 for Super-computational Life Science, grant-in-aid for MEXT/JSPS KAKENHI 19H03661, AMED grant number A368TS, Bristol-Myers Squibb for independent research support project (33999603), and the Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering and Vehicle Racing Commemorative Foundation for the grant (6236).

Abstract

The role of erythrocytes in platelet adhesion to von Willebrand factor (VWF) on the vessel wall through their membrane glycoprotein (GP)Ibα under blood flow conditions has not yet been elucidated. Blood specimens containing fluorescent-labeled platelets and native, biochemically fixed, or artificial erythrocytes at various hematocrits were perfused on the surface of VWF immobilized on the wall at a shear rate of 1,500 s−1. The rates of platelet adhesion were measured under each condition. The computer simulation of platelet adhesion to the VWF on the wall at the same shear rate was conducted by solving the governing equations with a finite-difference method on a K computer. The rates of platelet adhesion were calculated at various hematocrit conditions in the computational domain of 100 µm (x-axis) × 400 µm (y-axis) × 100 µm (z-axis). Biological experiments demonstrated a positive correlation between the rates of platelet adhesion and hematocrit values in native, fixed, and artificial erythrocytes. (r = 0.992, 0.934, and 0.825 respectively, p < 0.05 for all). The computer simulation results supported the hematocrit-dependent increase in platelet adhesion rates on VWF (94.3/second at 10%, 185.2/second at 20%, and 327.9/second at 30%). These results suggest that erythrocytes play an important role in platelet adhesion to VWF. The augmented z-axis fluctuation of flowing platelets caused by the physical presence of erythrocytes is speculated to be the cause of the hematocrit-dependent increase in platelet adhesion.

Supplementary Material



Publication History

Received: 02 June 2021

Accepted: 24 October 2021

Accepted Manuscript online:
25 October 2021

Article published online:
29 December 2021

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