ACTIVATED ENDOTHELIAL ADHESIVITY IN SC VASOOCCLUSION

SC 血管闭塞中的活化内皮粘附力

• 批准号: 6527377
• 负责人: Stephen H. Embury
• 金额: $ 31.04万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-27 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527377
• 关键词: blood vessel occlusion; cell adhesion; cell adhesion molecules; cell line; clinical research; disease /disorder model; erythrocytes; fluorescence microscopy; gene targeting; genetically modified animals; human subject; intravital microscopy; laboratory mouse; sickle cell anemia; thrombin receptor; vascular endothelium

DESCRIPTION: (Adapted from investigator's abstract) This proposal focuses on the adhesogenic responses of endothelial cells to agonists germane to sickle cell disease. The specific aims are to test the following hypotheses: 1) that thrombin and hypoxia (I/R) enhance EC adhesivity for SS RB; 2) that specific EC adhesive molecules account for increased adhesivity; and 3) that identifiable cellular mechanisms account for the increased adhesivity. Aims 1 and 2 will be studied in vitro and, using a mouse model of sickle cell disease, in vivo. The singular focus on activated endothelial cell adhesivity provides an innovative perspective to this proposal. The availability of a transgenic knockout sickle cell mouse model highly concordant with the human disease and of a state-of-the-art intravital microscopy system provide an exceptional opportunity to verify in vivo the importance of in vitro adherence phenomena. These experiments are anticipated to enhance our understanding of the molecular mechanisms of sickle erythrocyte-endothelial adherence, improve our grasp of the pathophysiology of sickle cell vasoocclusion, and expand our knowledge of endothelial cell biology. They may provide the basis for future therapeutic interventions.

描述：（改编自研究者的摘要）该提案的重点是 内皮细胞对与镰刀密切相关的激动剂的粘附反应 细胞疾病。具体目标是检验以下假设：1） 凝血酶和缺氧 (I/R) 增强 SS RB 的 EC 粘附性； 2）特定的EC 粘合剂分子增加了粘合力； 3）可识别的 细胞机制解释了粘附性的增加。目标 1 和 2 将是 体外研究，并使用镰状细胞病小鼠模型进行体内研究。这 对活化内皮细胞粘附性的单一关注提供了一种创新 对此提案的看法。转基因敲除镰刀的可用性 细胞小鼠模型与人类疾病高度一致 最先进的活体显微镜系统提供了卓越的 有机会在体内验证体外粘附现象的重要性。 这些实验预计将增强我们对分子的理解 镰状红细胞-内皮粘附机制，提高我们对 镰状细胞血管闭塞的病理生理学，并扩展我们的知识 内皮细胞生物学。它们可能为未来的治疗提供基础 干预措施。