Abstract
Several serpins function as potent inhibitors of thrombolytic serine proteases. Venous thrombosis is a common and debilitating condition whose incidence is on the rise. Studies using genetically modified mice and inhibitors have shown that the plasminogen activator inhibitors (PAI), PAI-1 and PAI-2, are primary regulators of plasminogen activation and contribute to regulating the resolution of experimental venous thrombi, via inflammatory mechanisms, vascular remodeling, and inhibition of fibrinolysis. Therapies to accelerate venous thrombus resolution would be beneficial, since delayed or incomplete clot resolution frequently leads to postthrombotic syndrome, a long-term complication associated with debilitating limb swelling, pain, and recurrent skin ulceration. Here we describe a useful and reproducible mouse model for the study of venous thrombus resolution involving ligation of the inferior vena cava and elucidation of the molecular and cellular determinants of venous thrombus formation and resolution.
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Acknowledgments
This work was supported by award number 1I01BX001921 (TMA) from the Biomedical Laboratory Research & Development Service of the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and by the National Institutes of Health T32 HL007698 (TAJ).
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Mukhopadhyay, S., Johnson, T.A., Sarkar, R., Antalis, T.M. (2018). Serpins in Venous Thrombosis and Venous Thrombus Resolution. In: Lucas, A. (eds) Serpins. Methods in Molecular Biology, vol 1826. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8645-3_13
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DOI: https://doi.org/10.1007/978-1-4939-8645-3_13
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