Thrombus resolution is CXC chemokine dependent

描述（由申请人提供）： 长期目标：拟议的研究，加上密切指导 实验室指导、研讨会和课程工作将大大拓宽 申请人的科学教育，并导致一个独立的调查员 status. 研究：与大多数动脉血管疾病不同，静脉血栓性疾病 除抗凝治疗外，缺乏持续有效的治疗方法 预防和治疗。深静脉血栓形成的解决包括 炎症介质和类似于伤口愈合的细胞反应 过程趋化因子是许多炎症过程的核心。的CXC 亚家族是PMNs主要化学引诱剂和激活剂， 直接促血管生成。 该提案将利用细胞培养和两种DVT的小动物模型， 回答以下具体目标：1）确定CXC趋化因子的作用 及其效应白细胞对深静脉血栓形成的分子和细胞作用 2）确定CXC趋化因子对中性粒细胞的体外作用， 衍生的血管溶解和血管生成介质，和3）确定作用 和外源性促血管生成和抑制血管生成的CXC的作用 趋化因子对生理性深静脉血栓形成消退的影响。分子 生物学、免疫学以及体外和体内血管生成 生物测定，结合生理测定，将用于实现 高于目标。定义基础趋化因子介导的DVT消退 病理生理学将潜在地产生基于药理学或细胞学的 加速DVT消退以减少血栓周围炎症的疗法， 减少静脉壁损伤，降低肺栓塞风险。

DESCRIPTION (provided by applicant): Long term objectives: The proposed studies, coupled with closely mentored laboratory guidance, seminars and course work will significantly broaden the applicant's scientific education and lead to an independent investigator status. Research: Unlike much arterial vascular disease, venous thrombotic disease lacks a consistently effective therapeutic approach outside of anticoagulation prophylaxis and treatment. Deep venous thrombosis resolution involves inflammatory mediator and cellular responses similar to the wound healing process. Chemokines are central to many inflammatory processes. The CXC subfamily are primary chemoattractants and activators of PMNs, and are directly proangiogenic. This proposal will utilize cell culture and two small animal models of DVT to answer the following specific aims: 1) To define the role of CXC chemokines and their effector leukocytes on molecular and cellular deep vein thrombosis resolution, 2) To determine the in vitro role of CXC chemokines on neutrophil derived fibrincilytic and angiogenic mediators, and 3) To determine the role of neutrophils and the effect of exogenous proangiogenic and angiostatic CXC chemokines on physiological deep vein thrombosis resolution. Molecular biological, immunological, as well as in vitro and in vivo angiogenesis bioassays, in conjunction with physiologic assays, will be used to achieve the above aims. Defining the basic chemokine mediated DVT resolution pathophysiology will potentially yield phamacologic or cellular based therapies to hasten DVT resolution for decreased peri-thrombotic inflammation, decreased vein wall damage, and decreased risk of pulmonary embolism.