ACTIVATED ENDOTHELIAL ADHESIVITY IN SC VASOOCCLUSION

SC 血管闭塞中的活化内皮粘附力

• 批准号: 6390650
• 负责人: Stephen H. Embury
• 金额: $ 30.11万
• 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/6390650
• 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：（根据调查员的摘要进行了改编）该提案的重点是 内皮细胞对激动剂的粘附反应对镰刀 细胞疾病。具体目的是检验以下假设：1） 凝血酶和缺氧（I/R）提高了SS RB的EC粘附； 2）特定的EC 粘合分子可以提高粘附性； 3）可识别的 细胞机制解释了粘附性的提高。目标1和2将是 在体外研究了体外的小鼠模型，并在体内研究。这 对激活的内皮细胞粘附的奇异关注提供了创新的 该提议的观点。转基因淘汰赛镰刀的可用性 细胞小鼠模型与人类疾病和A高度一致 最先进的插入显微镜系统提供了特殊的 在体内验证体外依从现象的重要性的机会。 预计这些实验可以增强我们对分子的理解 镰状红细胞 - 内皮依从性的机制，提高了我们对 镰状细胞血管牙合的病理生理学，并扩展我们对 内皮细胞生物学。他们可以为将来的治疗提供基础 干预措施。