Mechanism of cold storage lesion resistance in hibernating ground squirrel platelets

University Of Wisconsin La Crosse, La Crosse WI

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Abstract

Project Summary Hibernating ground squirrels have dramatically decreased heart rates (3-5 beats per minute) and blood flow, which should put them at risk of forming blood clots. In response, they have several adaptations during hibernation that prevent blood clotting, including 3-fold decreases in Factors VIII (FVIII) and IX (FIX), and 10- fold decreases in von Willebrand factor (vWF), neutrophils, and platelets. The Central Hypothesis ground squirrel platelets are resistant to in vivo and in vitro cold storage lesions with some changes in the platelet proteome. This could be due to a combination of altered signaling pathways, resistance to cold-induced cellular damage, and interactions with extracellular factors. This adaptation could be reflected in differential protein expression, signaling, and ligand binding of ground squirrel platelets stored in the cold either in vitro or in situ. In previous research, we found several candidate pathways that differ between human and ground squirrel platelets and also decreased cold induced activation of apoptosis-associated pathways in ground squirrels. The three Specific Aims of this proposal are to 1) determine which signaling pathways contribute to cold storage resistance, 2) determine how ground squirrel platelets resist cold storage lesions, and 3) determine the effect of extracellular storage conditions on platelets. This project is innovative because we are pioneering the use proteomic and metabolomic techniques to determine how ground squirrel platelets are resistant to cold storage lesions in platelets. This research could lead to medical advances to treat thrombocytopenia, store human platelets in the cold for transfusions, and regulate blood coagulation in cases of accidental or induced hypothermia.