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Mouse Complete Stasis Model of Inferior Vena Cava Thrombosis
Published on: June 15, 2011
Mouse complete stasis model of inferior vena cava thrombosis
Shirley K Wrobleski1, Diana M Farris, José A Diaz
1Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan, USA.
Insights
A mouse model for studying venous thromboembolism (VTE) is presented. While cost-effective and useful for genetic studies, its limitations include vessel size and reduced therapeutic agent efficacy due to lack of blood flow.
Area of Science:
- * Biomedical research
- * Vascular biology
- * Thrombosis modeling
Background:
- * Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant U.S. health concern with high morbidity and mortality.
- * VTE ranks as the third most common vascular disease, affecting approximately 900,000 individuals annually in the U.S., leading to 300,000 deaths.
- * A reliable in vivo animal model is crucial for understanding VTE mechanisms.
Purpose of the Study:
- * To evaluate the utility of the mouse complete stasis model of inferior vena cava thrombosis for VTE research.
- * To highlight the advantages and disadvantages of this mouse model for studying thrombosis.
- * To identify areas for improvement in VTE animal modeling.
Main Methods:
- * Utilization of a mouse model for inducing inferior vena cava thrombosis under complete stasis conditions.
- * Application of various molecular assays including RT-PCR, Western blot, ELISA, zymography, and cellular analysis.
- * Analysis of vein wall, thrombus, whole blood, and plasma samples.
Main Results:
- * The mouse model allows for cost-effective administration of small volumes of test agents and facilitates studies using gene knockout mice.
- * Current molecular assays can quantify components within the vein wall, thrombus, and blood.
- * Challenges include operative size constraints, vessel friability, and the need for increased animal numbers due to small sample sizes.
Conclusions:
- * The mouse complete stasis model offers advantages for studying VTE mechanisms, particularly with genetically modified mice and advanced molecular assays.
- * Limitations such as vessel size and lack of blood flow impact the assessment of systemic therapies.
- * Further refinement of animal models is necessary for comprehensive VTE research.
Abstract:
Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). In the United States (U.S.), the high morbidity and mortality rates make VTE a serious health concern (1-2). After heart disease and stroke, VTE is the third most common vascular disease (3). In the U.S. alone, there is an estimated 900,000 people affected each year, with 300,000 deaths occurring annually (3). A reliable in vivo animal model to study the mechanisms of this disease is necessary. The advantages of using the mouse complete stasis model of inferior vena cava thrombosis are several. The mouse model allows for the administration of very small volumes of limited availability test agents, reducing costs dramatically. Most promising is the potential for mice with gene knockouts that allow specific inflammatory and coagulation factor functions to be delineated. Current molecular assays allow for the quantitation of vein wall, thrombus, whole blood, and plasma for assays. However, a major concern involving this model is the operative size constraints and the friability of the vessels. Also, due to the small IVC sample weight (mean 0.005 grams) it is necessary to increase animal numbers for accurate statistical analysis for tissue, thrombus, and blood assays such as real-time polymerase chain reaction (RT-PCR), western blot, enzyme-linked immunosorbent (ELISA), zymography, vein wall and thrombus cellular analysis, and whole blood and plasma assays (4-8). The major disadvantage with the stasis model is that the lack of blood flow inhibits the maximal effect of administered systemic therapeutic agents on the thrombus and vein wall.

