University of Birmingham, UK
Posters & Accepted Abstracts: J Clin Exp Cardiolog
Thrombosis is a major health problem. Arterial thrombosis underlies such diseases as myocardial infarction and stroke. Venous thromboembolism (VTE) causes more deaths than breast cancer, acquired immunodeficiency syndrome and road traffic incidents, combined. However, mechanisms of thrombus development are still incompletely clear. Glycoprotein VI (GPVI) and CLEC-2 represent a family of immunoreceptor tyrosine-based activation motif (ITAM)-containing receptors. We investigated role of these receptors in thrombosis utilizing laser injury in cremaster muscle and a murine model of DVT based on stenosis of the inferior vena cava (IVC). Mice deficient for GPVI had a trend to decreased DVT incidence similarly to mice with antibody-depleted receptor. In the laser injury model, thrombi GPVI-deficient mice began to appear, but did not grow and quickly embolized. The resulting thrombus size was substantially less than in wild-type controls. In contrast, mice lacking CLEC-2 had normal thrombosis in the laser injury model, but were completely protected against DVT. Staining for the CLEC-2 ligand podoplanin did not reveal its expression after 48 h IVC stenosis. Using intra-vital microscopy of the IVC 6 h after application of stenosis we showed that platelet recruitment to the vessel wall was reduced. This implies suppressed endothelial activation and secretion of Weibel-Palade bodies, processes indispensable for DVT in this model. Bleeding time in CLEC-2 deficient mice was comparable with wild-type controls. In conclusion, we report here dissimilar functions of ITAM receptors in different models of thrombosis. CLEC-2 is implicated in DVT whereas GPVI is important for thrombus propagation in the laser injury model.
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