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，并导致独立调查人员 状态。 研究：与许多动脉血管疾病不同，静脉血栓性疾病 缺乏持续有效的抗凝以外的治疗方法 预防和治疗。深静脉血栓的解决包括 与伤口愈合相似的炎症介质和细胞反应 进程。趋化因子是许多炎症过程的中心。CXC 亚家族是PMN的主要趋化因子和激活剂，它们是 直接促血管生成。 这项提议将利用细胞培养和DVT的两个小动物模型来 回答以下具体目标：1)确定CXC趋化因子的作用 及其效应白细胞对分子和细胞深静脉血栓形成的影响 决议，2)确定CXC趋化因子对中性粒细胞的体外作用 衍生的纤溶和血管生成介质，以及3)确定其作用 中性粒细胞的变化及外源性促血管生成和抑血管活性CXC的作用 趋化因子对生理性深静脉血栓消退的影响。分子 生物学、免疫学以及体外和体内血管生成 生物化验与生理化验将结合使用来实现 在目标之上。确定基本趋化因子介导的DVT解决方案 病理生理学可能产生基于药理学或细胞学的 减少血栓周围炎症的加速深静脉血栓消退的治疗， 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.