CD39 AND PLATELET REACTIVITY IN ARTERIAL AND VENOUS THROMBOSIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 我们提出了一项对年轻的急性冠状动脉综合征（ACS）或自发性静脉血栓栓塞症（VTE）患者和健康对照者的横断面研究，以解决4个特定的目标：1）调查在急性期和恢复期的过早动脉粥样硬化患者中，CD 39活性降低和CD 39剪接变体1.5表达增加是否与ACS相关;（2）评价急性期和恢复期CD 39活性、CD 39亚型表达与自发性VTE之间的关系;（3）确定血小板反应性增加是否与自发性VTE相关以及相关程度，并将其程度与ACS进行比较; 4）评估血液中TF在过早动脉和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的潜在中心分子。CD 39缺陷在人类血栓形成中的作用将刺激对这种活性降低的决定因素的进一步研究，并为测试可溶性CD 39的治疗应用提供强有力的理由。新的治疗选择可以通过确定的作用，血液传播的TF在过早的动脉和静脉血栓形成的发病机制。最后，通过证明血小板活化是否以及在多大程度上参与了VTE，该研究可以适当地重新关注研究，并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.