Effects of Hibernation on Hemostasis in 13-lined Ground Squirrels
冬眠对十三行地松鼠止血的影响
基本信息
- 批准号:7515502
- 负责人:
- 金额:$ 18.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-07-07 至 2012-02-29
- 项目状态:已结题
- 来源:
- 关键词:AdhesionsAffectAnimalsAnticoagulantsArousalBackBiological AssayBlood ClotBlood Coagulation FactorBlood PlateletsBlood coagulationBlood flowChillsCoagulation ProcessDetectionDropsFactor IXFactor VIIIFibrinFibrin fragment DFibrinolysisHeart RateHemophilia AHemostatic functionHibernationHourHumanIn VitroLeadLifeLiverMammalsMeasuresMethodsMicrotubulesPathway interactionsPatientsPlasmaPlatelet Count measurementPlatelet aggregationProtein CProteinsProthrombin time assayPublic HealthPublishingRegulationResearchResistanceRiskSerpinsSpermophilusSpleenSurfaceTemperatureTestingThrombocytopeniaThrombomodulinTimeclinical applicationdaydirect applicationimprovedin vivoinduced hypothermianatural hypothermiaresponseretinal rods
项目摘要
DESCRIPTION (provided by applicant): Hibernating ground squirrels have dramatically decreased heart rates and blood flow which should put them at risk of forming blood clots. In response, they have several adaptations that decrease blood clotting, including a decrease in the levels of blood clotting factors VIII and IX, and a 90% decrease in platelets. The platelet decrease is due to reorganization of microtubules leading to a conformational change in the platelets causing them to be trapped in the spleen. Within two hours of arousal in the spring, platelet levels and blood clotting times return to normal. The specific aims of this proposal are to study the effects of hibernation on platelet activity, the regulation of blood clotting factors, and fibrinolysis, or the breakdown of fibrin clots. Platelet activity will be measured before, during an immediately after hibernation by detection of markers of activation on the surface of platelets and by platelet aggregation and adhesion. Human platelets that are stored in the cold are rapidly cleared by the liver when re-injected back into a patient. As ground squirrel platelets are essentially stored in the cold for six months while hibernating, we will test if this same mechanism occurs by injecting ground squirrels with warmed and chilled platelets and following their clearance in vivo. This could have direct application in extending storage of human platelets in the cold. Hibernation also reversibly reduces the activity of blood clotting factors VIII and IX, but not most of the other clotting factors. Understanding how these two clotting factors activities are reversibly regulated could lead to improved treatments of hemophilia A and B. Several other proteins that are known to regulate blood clotting have not been studied in hibernating animals, and could be additional candidate proteins to regulate blood clotting during periods of low blood flow. Finally, the impact of hibernation on the breakdown of blood clots has not been measured, and we will compare ground squirrel plasma before, during and immediately after hibernation for markers of fibrinolysis, like D-dimer, and the activity of proteins involved in fibrinolysis. This research will improve our understanding of how a mammal can adapt to reduce the risk of blood clots during low blood flow, and preserve platelet activity after hypothermia. These findings could have direct clinical applications in allowing human platelets to be stored in the cold, regulating blood coagulation in cases of accidental or induced hypothermia, and reversible regulation of factor VIII and IX activity. PUBLIC HEALTH RELEVANCE: This research could identify ways to store human platelets in the cold which would increase their shelf life. The research could also lead to treatments that reversibly regulate two important blood clotting factors, possibly as long-term anti-clotting therapy.
描述(由申请人提供):冬眠的地松鼠会显著降低心率和血流量,这将使它们有形成血栓的风险。作为回应,它们有几种减少血液凝固的适应性,包括血液凝固因子VIII和IX水平的降低,血小板减少90%。血小板减少是由于微管的重组导致血小板的构象改变,导致它们被困在脾脏中。在春天醒来的两个小时内,血小板水平和凝血时间就会恢复正常。这项提议的具体目的是研究冬眠对血小板活性的影响,血液凝固因子的调节,以及纤维蛋白溶解或纤维蛋白凝块的分解。通过检测血小板表面的活化标记物以及血小板聚集和粘附,在冬眠前、冬眠中和冬眠后立即测量血小板活性。储存在低温环境中的人类血小板在重新注射回病人体内时,会被肝脏迅速清除。由于地松鼠的血小板在冬眠时基本上是在寒冷中储存6个月,我们将通过给地松鼠注射加热和冷却的血小板,并观察它们在体内的清除情况,来测试是否会发生同样的机制。这可以直接应用于延长人类血小板在低温下的储存。冬眠也会可逆地降低凝血因子VIII和IX的活性,但不会降低大多数其他凝血因子的活性。了解这两种凝血因子的活性是如何被可逆调节的,可能会改善血友病A和b的治疗方法。一些已知的调节血液凝固的其他蛋白质尚未在冬眠动物中进行研究,可能是在低血流量期间调节血液凝固的额外候选蛋白质。最后,冬眠对血凝块分解的影响还没有被测量,我们将比较冬眠前、冬眠中和冬眠后的地鼠血浆中纤维蛋白溶解的标志物,如d -二聚体,以及参与纤维蛋白溶解的蛋白质的活性。这项研究将提高我们对哺乳动物如何适应在低血流量时降低血栓风险,并在体温过低后保持血小板活性的理解。这些发现可能有直接的临床应用,允许人类血小板在寒冷中储存,在意外或诱发的低体温情况下调节血液凝固,以及可逆调节因子VIII和IX的活性。公共卫生相关性:这项研究可以确定在寒冷中储存人类血小板的方法,从而延长其保质期。这项研究还可能导致对两种重要的凝血因子进行可逆调节的治疗方法,可能是长期的抗凝血疗法。
项目成果
期刊论文数量(0)
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SCOTT T COOPER其他文献
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{{ truncateString('SCOTT T COOPER', 18)}}的其他基金
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 - 财政年份:2008
- 资助金额:
$ 18.5万 - 项目类别:
Effects of Hibernation on Hemostasis in 13-lined Ground Squirrels
冬眠对十三行地松鼠止血的影响
- 批准号:
8227401 - 财政年份:2008
- 资助金额:
$ 18.5万 - 项目类别:
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