ADVENTITIA AND VASCULAR LESION FORMATION

描述（改编自研究者摘要）：研究者 假设富含成纤维细胞的外膜， 在血管成形术后血管病变形成和 动脉粥样硬化过程 最近的数据表明，主要的反应 血管成形术后立即发生外膜炎症， 外膜肌成纤维细胞增殖。 假设这些 反应部分是由外膜血液供应的减少刺激的 由球囊膨胀引起的血管扩张导致外膜 缺血 他的工作暗示血管成形术的一个结果可能是 血管成形术再狭窄可能不仅仅是由机械损伤引起的， 动脉粥样硬化斑块和/或内侧壁。 来自博士的更多数据 Wilcox的实验室表明，外膜肌成纤维细胞具有 血管成形术后可能迁移到新生内膜， 再狭窄病变的质量。 为了实现具体目标， 申请人设计了在良好限定的气球模型中的新实验 使用猪冠状动脉的过度拉伸损伤。 这些研究将 确定外膜肌成纤维细胞迁移到 再狭窄病变，球囊引起的外膜缺血程度 膨胀，以及其对外膜中纤维化和炎症的影响。 现已设计了四个具体目标来解决悬而未决的问题 这一领域的问题以及以前的审查员的问题。 首先，申请人将确定外膜的贡献 肌成纤维细胞的再狭窄的发展。 其次，他将学习 缺血在刺激外膜炎症和纤维化中的作用。 申请人特别感兴趣的是缺血对ICAM的影响 外膜IL-8表达。 第三，假设 血管成形术导致外膜血流减少， 将测试局部缺血。 最后，主要研究者将确定 与血管成形术相关的外膜炎症在 损伤后血管壁的早期生长反应。

DESCRIPTION (Adapted from Investigator's Abstract): The investigator hypothesizes that the adventitia which is enriched in fibroblasts, plays a major role in vascular lesion formation after angioplasty and during the atherosclerosis process. Recent data indicate that the major responses immediately after angioplasty are inflammation of the adventitia and proliferation of adventitial myofibroblasts. The hypothesis is that these responses are stimulated, in part, by a reduction of adventitia blood supply by the vasa vasorum caused by balloon inflation resulting in adventitia ischemia. His work implies that one result of angioplasty may be that post angioplasty restenosis may not be caused solely by a mechanical injury of the atherosclerotic plaque and / or medial wall. Additional data from Dr. Wilcox's laboratory indicate that adventitia myofibroblasts have the potential to migrate into the neointima after angioplasty and contribute to the mass of the restenotic lesion. To address the specific aims, the applicant has designed new experiments in a well defined model of balloon overstretched injury using porcine coronary arteries. These studies will determine the extent of adventitia myofibroblast migration into the restenotic lesion, the extent of the adventitia ischemia caused by balloon inflation, and its effects on fibrosis and inflammation in the adventitia. Four specific aims have now been designed to address the unanswered questions in this field as well as those of the previous reviewers. Firstly, the applicant will determine the contribution of adventitial myofibroblasts to the development of restenosis. Secondly, he will study the role of ischemia in stimulating adventitial inflammation and fibrosis. The applicant is particularly interested in the effect of ischemia on ICAM and IL-8 expression in the adventitia. Thirdly, the hypothesis that angioplasty causes a reduction of adventitia blood flow resulting in ischemia will be tested. Finally, the Principal Investigator will determine the role of adventitia inflammation which is associated with angioplasty in the early growth responses in the vascular wall after injury.