Potential different impact of inhibition of thrombin function and thrombin generation rate for the growth of thrombi formed at site of endothelial injury under blood flow condition

Ayabe, Kengo; Goto, Shinichi; Oka, Hideki; Yabushita, Hiroto; Nakayama, Masamitsu; Tomita, Aiko; Hasebe, Terumitsu; Yokota, Hideo; Takagi, Shu

doi:10.1016/j.thromres.2019.05.007

Cited by 8 publications

(4 citation statements)

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“…4 A more systematic evaluation for both formation, decay, and location of thrombin may better reflect risks of thrombotic diseases. 5 Non-invasive molecular imaging techniques provide attractive strategies for identification of thrombosis by targeting specific structures of fibrin, activated platelets, or coagulation enzymes such as thrombin. Accurate and spontaneous detection of thrombosis is highly desirable to minimize the risks of acute myocardial infarction (AMI), stroke, and VTE.…”

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confidence: 99%

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A Thrombin-Responsive Nanoprobe for In Vivo Visualization of Thrombus Formation through Three-Dimensional Optical/Computed Tomography Hybrid Imaging

Wang

Yang

et al. 2021

ACS Appl. Mater. Interfaces

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Early spontaneous detection of thrombin activation benefits precise theranostics for thrombotic vascular disease. Herein, a thrombin-responsive nanoprobe conjugated by a FITC dye, PEGylated Fe 3 O 4 nanoparticles, and a thrombin-sensitive peptide (LASG) was constructed to visualize thrombin activation and subsequent thrombosis in vivo. The FITC dye was linked to the LASG coated on the Fe 3 O 4 nanoparticles for sensing the thrombin activity via the Forster resonance energy transfer effect. In vitro fluorescence imaging showed that the fluorescence signal intensity increased significantly after incubation with thrombin in contrast to that of the control group (p < 0.05), and the signal intensity was enhanced with the increase in thrombin concentration. Further in vivo fluorescence imaging also revealed that the signal elevated markedly in the left common carotid artery (LCCA) lesion of the mice thrombosis model after nanoprobe injection, in contrast to that of the control + nanoprobe group (p < 0.05). Moreover, the thrombin inhibitor bivalirudin could decrease the filling defect of the LCCA. Three-dimensional fusion images of micro-CT and fluorescence confirmed that filling defects in the LCCA were nicely colocalized with fluorescence signal caused by nanoprobes. The nanoplatform based on a thrombin-activatable visualization system could provide smart responsive and dynamic imaging of thrombosis in vivo.

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confidence: 99%

“…These approaches are applied for ex vivo screening coagulation activity from the blood sample, which was not accurate for predicting intravascular in situ thrombosis events . A more systematic evaluation for both formation, decay, and location of thrombin may better reflect risks of thrombotic diseases …”

mentioning

confidence: 99%

A Thrombin-Responsive Nanoprobe for In Vivo Visualization of Thrombus Formation through Three-Dimensional Optical/Computed Tomography Hybrid Imaging

Wang

Yang

et al. 2021

ACS Appl. Mater. Interfaces

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“…26 This part is unique because previously published simulation models considered the influence of platelet activation and the involvement of GPIIb/IIIa for platelet adhesion on the VWF wall. 7 38 39 The validity of our simulation with regard to erythrocyte deformities and movements was confirmed by intravital microscopic visualization of capillary circulation in mice. 40 The higher rate of platelet adhesion in the presence of erythrocytes at higher hematocrit values shown here reflected increased z -axis fluctuation of platelets close to the VWF wall under blood flow conditions.…”

Section: Discussionmentioning

confidence: 57%

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

et al. 2021

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The roles of erythrocytes on platelet adhesion to von Willebrand factor (VWF) on the vessel wall through their membrane glycoprotein (GP)Ibα under blood flow condition is still to be elucidated. Blood specimens containing fluorescently labeled platelet and native, biochemically fixed, or artificial erythrocytes, at various hematocrits were perfused on a surface of VWF immobilized on the wall at a shear rate of 1,500 s-1. Rates of platelet adhesions were measured in each condition. Computer simulation of platelet adhesion to the VWF on the wall at the same shear rate was conducted by solving governing equations with a finite-difference method on K-computer. The rates of platelet adhesion were calculated at various hematocrits conditions in the computational domain of 100 µm (x-axis) x 400 µm (y-axis) x 100 µm (z-axis). Biological experiments demonstrated the 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/sec at 10%, 185.2/sec at 20%, and 327.9/sec at 30%, respectively). These results suggest the important contributing role of erythrocytes on platelet adhesion to the VWF. The augmented z-axis fluctuation of flowing platelet caused by the physical presence of erythrocytes is speculated as the cause for hematocrit dependent increase in platelet adhesion.

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“…The process of thrombus formation at the site of endothelial injury is complex. We have attempted to develop the process model of thrombus formation as shown in Figure 4 [32]. The model is still simple but includes various physically and chemically different events.…”

Section: Activation Of Coagulation Cascade and Fibrinolysismentioning

confidence: 99%

Mechanism of Thrombus Formation in Regard to Diet

Goto¹

2021

New Insights Into Metabolic Syndrome

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The majority of diseases causing sudden death or sudden onset of serious restriction of quality of life are thrombotic disease. Myocardial infarction is often caused by thrombotic occlusion of coronary arterial branches. Ischemic stroke is also caused by occlusion of cerebral arteries with thrombi. In patients admitted to the hospital and immobility, venous thromboembolism causing pulmonary embolism is a major cause of death. The risk of cardiovascular events is influenced by food intake. Yet, the mechanism between specific food intake and the risk of thrombotic disease is still to be elucidated. Recent progress of computer and information technology allows us to describe complex biological phenomena such as thrombosis from basic principles of physics and chemistry. Coupling blood flow, platelet, coagulation, and fibrinolysis allows us to understand the contributing role of each factor for thrombus formation. Yet, the precise role of food intake to influence the risk of thrombosis is still to be elucidated. Coupling basic research and large-scale clinical research will further clarify the role of various types of food intake in the risk of thrombosis.

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Potential different impact of inhibition of thrombin function and thrombin generation rate for the growth of thrombi formed at site of endothelial injury under blood flow condition

Cited by 8 publications

References 45 publications

A Thrombin-Responsive Nanoprobe for In Vivo Visualization of Thrombus Formation through Three-Dimensional Optical/Computed Tomography Hybrid Imaging

A Thrombin-Responsive Nanoprobe for In Vivo Visualization of Thrombus Formation through Three-Dimensional Optical/Computed Tomography Hybrid Imaging

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

Mechanism of Thrombus Formation in Regard to Diet

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