CD39 AND PLATELET REACTIVITY IN ARTERIAL AND VENOUS THROMBOSIS

动脉和静脉血栓形成中的 CD39 和血小板反应性

• 批准号: 7604159
• 负责人: JORGE R KIZER
• 金额: $ 0.02万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604159
• 关键词: Acute; Address; Atherosclerosis; Blood; Blood Platelets; Computer Retrieval of Information on Scientific Projects Database; Cross-Sectional Studies; Funding; Grant; Human; Institution; Pathogenesis; Patients; Phase; Platelet Activation; Protein Isoforms; RNA Splicing; Research; Research Personnel; Resources; Role; Source; Testing; Therapeutic; Thromboembolism; Thrombosis; United States National Institutes of Health; Variant; Venous; Venous Thrombosis; acute coronary syndrome; novel therapeutics

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们建议对患有急性冠脉综合征 (ACS) 或自发性静脉血栓栓塞 (VTE) 的年轻患者和健康对照者进行一项横断面研究，以实现 4 个具体目标：1) 调查 CD39 活性是否降低以及 CD39 剪接变体 1.5 的表达是否增加，与早发动脉粥样硬化患者的 ACS 相关，无论是在急性期还是在恢复期； 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加是否以及在何种程度上与自发性 VTE 相关，并将其程度与 ACS 中的相关程度进行比较； 4) 评估血源性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潜在的核心分子。 CD39 缺乏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进行更多研究，并为测试可溶性 CD39 的治疗应用提供强有力的理由。通过确定血源性 TF 在过早动脉和静脉血栓形成发病机制中的作用，可以开辟新的治疗选择。最后，通过证明血小板激活是否以及在何种程度上参与 VTE，该研究可以适当地重新调整研究重点，并具有明确的治疗意义。