Date of Award
Master of Science
Theodore Kent Gartner
Carlos E Lopez-Estrano
Venous thromboembolism (VTE) is the leading cause of death from cardiovascular disease. Despite the importance of the glycoprotein (GP) Ib-IX/von Willebrand factor (VWF) axis in arterial thrombosis, its requirement in venous, not venule thrombosis has not been tested. We evaluated FeCl3-induced thrombus formation in inferior vena cava (IVC) of mice. We first established FeCl3 injury conditions (20% FeCl3, 10 minutes) requiring platelets for IVC occlusion as confirmed by a lack of occlusion in severely thrombocytopenic ( less than 23% circulating platelet count) mice (n=7) and stable occlusion in control animals. Using similar injury conditions, no IVC occlusion was observed using platelet GPIbα-deficient animals (n=6), a model of human Bernard-Soulier syndrome (BSS). Transgenic IL-4R/GPIbα mice were studied to determine if the absence of IVC occlusion in the mouse model of BSS was caused by extracellular GPIbα deficiency or by other platelet abnormalities associated with BSS phenotype. IL-4R/GPIbα mice lack murine GPIbα, but express a transgenic fusion protein compound of an extracellular domains of human IL-4 receptor fused to the transmembrane and cytoplasmic domains of human GPIbα ; an ameliorated form of mouse BSS lacking macrothrombocytopenia. No occlusion was observed in the IVC of IL-4R/GPIbα mice (n=8), just as observed with the murine model of BSS. VWF-deficient mice were also studied and failed to occlude in response to FeCl3 treatment (n=7). These data establish experimental conditions for FeCl3-induced thrombus formation in the IVC that is platelet, platelet receptor GPIbα and VWF-dependent despite the low venous flow rate in the IVC. Also unlike venules, thrombus formation in IVC’s is GPIb-IX dependent, and fibronectin cannot substitute for VWF in IVC’s as it can in arterioles.
dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.
Joglekar, Manali Vinay, "Ferric chloride-induced thrombus formation in murine inferior vena cava requires platelets, platelet receptor GPIb-IX and von Willebrand factor" (2010). Electronic Theses and Dissertations. 51.