CD39 AND PLATELET REACTIVITY IN ARTERIAL AND VENOUS THROMBOSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们建议对年轻的急性冠脉综合征(ACS)或自发性静脉血栓栓塞症(VTE)患者和健康对照组进行横断面研究，以解决4个特定目标：1)研究CD39活性降低和CD39剪接变体1.5表达增加是否与动脉粥样硬化过早患者急性期和恢复期的ACS相关；2)评估急性期和恢复期CD39活性、CD39亚型表达和自发性VTE之间的关系；3)确定血小板反应性增强是否以及在多大程度上与自发性VTE相关，并将其程度与ACS的程度进行比较；4)评价血源性转铁蛋白在动静脉血栓形成中的作用。 这项研究的意义在于它解决了人类血栓调节和血栓形成中潜在的中心分子。CD39缺乏在人类血栓形成中的作用将促使对这种活性降低的决定因素进行更多的研究，并为检测用于治疗应用的可溶性CD39提供强有力的理论基础。通过确定血源性转铁蛋白在动脉和静脉过早血栓形成的发病机制中的作用，可以开辟新的治疗方案。最后，通过证明血小板激活是否以及在多大程度上与VTE有关，这项研究可以适当地重新聚焦研究，具有明确的治疗意义。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose a cross-sectional study of younger patients with acute coronary syndromes (ACS) or spontaneous venous thromboembolism (VTE) and healthy controls to address 4 specific aims: 1) Investigate whether reduced CD39 activity, and increased expression of CD39 splice variant 1.5, are associated with ACS in patients with premature atherosclerosis, both in the acute and convalescent phases; 2) Evaluate relationship between CD39 activity, CD39 isoform expression, and spontaneous VTE, both in the acute and convalescent phases; 3) Determine whether, and to what degree, increased platelet reactivity is associated with spontaneous VTE, and to compare its extent to that in ACS; 4) Assess the role of blood-borne TF in premature arterial and venous thrombosis. The significance of this study is that it addresses potentially central molecules in human thromboregulation and thrombogenesis. A role for CD39 deficiency in human thrombosis would spur additional study into determinants of this reduced activity, and provide a strong rationale for testing soluble CD39 for therapeutic application. Novel therapeutic options could be opened by determining the role of blood-borne TF in the pathogenesis of premature arterial and venous thrombosis. Last, by demonstrating whether, and to what extent, platelet activation is involved in VTE, the study could re-focus research appropriately, with clear therapeutic implications.