Murine thrombosis models

Day, Sharlene M.; Reeve, Jennifer; Myers, Daniel D.; Fay, William P.

doi:10.1055/s-0037-1613739

Cited by 104 publications

(80 citation statements)

References 30 publications

(34 reference statements)

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“…Mice were infused through the jugular vein with either saline (vehicle) or integrilin (10 mg/kg, a dose effective in the mouse model [1]) 5 min before injury. Clopidogrel was used at 50 mg/kg (administered orally twice into mice by gavage, the day before and 2 h before the experiment), a dose leading to a complete irreversible inhibition of the P 2 Y 12 receptor [16].…”

Section: Drug Administrationmentioning

confidence: 99%

“…More importantly, in vivo models, which can mimic the unavoidable mechanical injury resulting from stent deployment or balloon intervention, may provide a theoretical basis for improving the anti-thrombotic property of interventional materials. By utilizing various methods, researchers have developed many thrombosis models in the mouse to mimic human vascular disease [1]. These methods include chemical injury by ferric chloride (FeCl 3 ) of the carotid [2][3][4], laser-induced injury of the cremaster or mesenteric arteries [5][6][7][8][9], electric injury of the carotid artery [10], and mechanical injury through arterial compression, ligation, or introduction of a guidewire [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Thrombosis Model in Mouse Carotid Induced by Guidewire

et al. 2016

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Researchers have developed many thrombosis models in the mouse. Some methods for establishing the model require specialized equipment and have high cost. The present study develops a low-cost, easy-to-operate, and well-controlled vascular injury thrombosis model in the mouse carotid artery induced by a guidewire. Superficial injury was induced in the carotid artery by scratching with a guidewire. Thrombus formation was observed and recorded in real time. Thrombosis quantification analyses were performed using Metamorph and Graphpad software. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), and hematoxylin and eosin (HE) staining were employed for the histological analysis of the injured vessel wall. Three clinical drugs were respectively administrated to this model for further evaluation. Complete removal of the endothelium was observed by TEM in this injury model. Platelets covered the denuded surface, in which the aggregates were detected by HE staining and SEM. A transient thrombus reaching peak at around 1 min after injury and vanishing gradually within 3 min formed in the model. Administration of clinical medicaments decreased thrombus formation in this model. All lesions were sensitive to platelet GPIIb-IIIa, P2Y12 inhibition, and thrombin blockade. The proposed model has good reproducibility and feasibility and could be applied in therapeutic targeting and anti-thrombotic drug screening.

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Section: Drug Administrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thrombosis Model in Mouse Carotid Induced by Guidewire

et al. 2016

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“…For this purpose, an FeCl 3 -induced mouse carotid artery thrombosis model was constructed and tested ( Figure 7A). 30 Different from the lung thrombosis model, the thrombosis in this model is in the systemic circulation. Also, the clotting cascade is triggered differently, by docking of ferric ions onto endothelialassociated red blood cells.…”

Section: Articlementioning

confidence: 99%

Clot-Targeted Micellar Formulation Improves Anticoagulation Efficacy of Bivalirudin

et al. 2014

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Application of anticoagulants remains the primary strategy for prevention and treatment of thrombosis. However, high rate of bleeding complications limits their use. The peptide anticoagulant bivalirudin has been reported to exhibit a lower rate of bleeding complications than heparin, and it also has the advantage of not causing thrombocytopenia, which is a problem with heparin. Nonetheless, hemorrhage is the most common complication of bivalirudin therapy, and there is no effective antidote. Here we use a thrombus-binding peptide, CR(NMe)EKA, to accomplish selective delivery of the bivalirudin-carrying micellar nanocarrier to sites of thrombosis. Bivalirudin and CR(NMe)EKA, each with a PEG-lipid tail, spontaneously assembled into 30 nm micelles, which almost completely retained the anticoagulant activity of bivalirudin. The micellar formulations exhibited high stability both in vitro and in vivo. In a thromboplastin-induced mouse thrombosis model, the targeted micelles accumulated in lung thrombi 10-fold more than nontargeted micelles. Moreover, the micellar formulation significantly prolonged the half-life and thereby increased the bioavailability of bivalirudin. The micellar bivalirudin had significantly higher anticoagulant activity than free bivalirudin in both the lung thrombosis model and a ferric chloride-induced carotid artery thrombosis model. The specific targeting of thrombi demonstrated here makes it possible to increase the efficacy of bivalirudin as an anticoagulant. Alternatively, the dose could be reduced without loss of efficacy to lower the systemic exposure and improve safety.

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“…Table (1) summarizes various experimental models of thrombosis that have been developed and used for thrombosis research and drug discovery in mice. Some experimental details and their utilities of these experimental models have been recently reviewed [17]. Among these experimental models, ferric chloride (FeCl 3 )-induced arterial thrombosis is one of the most widely used models in a number of species including mice, rats, and rabbits, since its initial description by Kurtz et al [4,17,18].…”

Section: Experimental Model Of Ferric Chloride-induced Arterial Thrommentioning

confidence: 99%

Experimental Mouse Models of Thrombosis Optimized for Drug Discovery and Development

Wang¹

2005

LDDD

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Animal models of diseases are essential for drug discovery and development. The availability of a large number of genetically-manipulated mice renders considerable interest in drug discovery by means of experimental models of disease. Ferric chloride-induced thrombosis is one of the most commonly used experimental models of thrombosis in mice. This review provides examples of optimizing this arterial thrombosis model for target validation and drug discovery in mice.

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Murine thrombosis models

Cited by 104 publications

References 30 publications

Thrombosis Model in Mouse Carotid Induced by Guidewire

Thrombosis Model in Mouse Carotid Induced by Guidewire

Clot-Targeted Micellar Formulation Improves Anticoagulation Efficacy of Bivalirudin

Experimental Mouse Models of Thrombosis Optimized for Drug Discovery and Development

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