Mechanism of cold storage lesion resistance in hibernating ground squirrel platelets

冬眠地松鼠血小板耐冷损伤的机制

• 批准号: 10730617
• 负责人: SCOTT T COOPER
• 金额: $ 33.5万
• 依托单位: UNIVERSITY OF WISCONSIN LA CROSSE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-07 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10730617
• 关键词: Accidents; Affect; Apoptosis; Apoptosis Inhibitor; Autophagocytosis; Biological Assay; Biological Process; Blood; Blood Platelets; Blood coagulation; Blood flow; Body Temperature; Cell physiology; Circulation; Coagulation Process; Cryopreservation; Environment; Factor IX; Factor VIII; Fluorescence; Fluorescence Resonance Energy Transfer; Generations; Grant; Heart; Heart Rate; Hemostatic function; Hibernation; Human; In Situ; In Vitro; Induction of Apoptosis; Lesion; Ligand Binding; Liver; Mammals; Measures; Medical; Methods; Microscopic; Mission; National Heart, Lung, and Blood Institute; Outcome; Pathway interactions; Phosphoproteins; Phosphorylation; Physiological; Physiological Adaptation; Plasma; Platelet Transfusion; Proteome; Proteomics; Research; Resistance; Risk; Signal Pathway; Signal Transduction; Spermophilus; Strategic vision; Techniques; Temperature; Thrombocytopenia; Thrombosis; Tissues; Transfusion; cell injury; clinically relevant; cold temperature; extracellular; improved; in vivo; induced hypothermia; inhibitor; innovation; metabolome; metabolomics; neutrophil; novel; preservation; prevent; protein expression; resilience; resistance mechanism; response; thrombotic; undergraduate student; von Willebrand Factor

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.

项目摘要 冬眠的地松鼠会显著降低心率（每分钟3-5次）和血流量， 这会让他们有形成血栓的危险作为回应，它们在 冬眠，防止血液凝固，包括因子VIII（FVIII）和IX（FIX）减少3倍， 血管性血友病因子（vWF）、中性粒细胞和血小板减少倍数。中心假设的基础 松鼠血小板对体内和体外冷藏损伤具有抗性， 蛋白质组这可能是由于改变的信号通路，对冷诱导细胞的抵抗， 损伤以及与细胞外因子的相互作用。这种适应性可以在差异蛋白质中反映出来 体外或原位低温储存的黄鼠血小板的表达、信号传导和配体结合。 在以前的研究中，我们发现了几个人类和地松鼠之间不同的候选途径 血小板，并减少了冷诱导激活的黄鼠的骨化相关途径。 该提案的三个具体目标是：1）确定哪些信号通路有助于寒冷 储存抗性，2）确定地松鼠血小板如何抵抗冷储存损伤，和3）确定 细胞外储存条件对血小板的影响。这个项目是创新的，因为我们是先锋 使用蛋白质组学和代谢组学技术来确定地松鼠血小板如何抵抗寒冷 血小板储存损伤。这项研究可能会导致医学进步，以治疗血小板减少症，储存 人血小板在寒冷的输血，并调节血液凝固的情况下，意外或诱导 体温过低

项目成果

Platelets from 13-lined ground squirrels are resistant to cold storage lesions.

13 系地松鼠的血小板对冷藏损伤具有抵抗力。

• DOI: 10.1007/s00360-022-01469-y
• 发表时间: 2023
• 期刊: Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology
• 作者: Splinter,N;Mancosky,A;Laffin,C;Clement,M;Nisius,M;Arbs,B;BonoAnno,E;Bartig,E;Cooper,S
• 通讯作者: Cooper,S

Cardiovascular resistance to thrombosis in 13-lined ground squirrels.

• DOI: 10.1007/s00360-018-1186-x
• 发表时间: 2019-03
• 期刊: Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology
• 作者: Bonis A;Anderson L;Talhouarne G;Schueller E;Unke J;Krus C;Stokka J;Koepke A;Lehrer B;Schuh A;Andersen JJ;Cooper S
• 通讯作者: Cooper S