ADVENTITIA AND VASCULAR LESION FORMATION

外膜和血管病变形成

• 批准号: 6056402
• 负责人: JOSIAH N WILCOX
• 金额: $ 29.84万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6056402
• 关键词: blood flow measurement; cell adhesion molecules; cell migration; fibroblasts; fibrosis; inflammation; interleukin 8; intraluminal angioplasty; ischemia; medical complication; restenosis; swine

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.

描述(改编自《调查员摘要》)：调查员 假设富含成纤维细胞的外膜在 在血管成形术后和血管成形术期间血管病变形成中的主要作用 动脉粥样硬化过程。最近的数据表明，主要的反应是 血管成形术后立即出现外膜炎症和 外膜肌成纤维细胞的增殖。假设是这些 外膜供血减少在一定程度上刺激了反应。 由血管球囊扩张引起的血管外膜 缺血症。他的研究表明，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于机械损伤引起的 动脉粥样硬化斑块和/或内侧壁。来自Dr。 Wilcox的实验室表明，外膜肌成纤维细胞具有 血管成形术后迁移到新生内膜的可能性并有助于 再狭窄病变的肿块。为了解决具体目标， 申请者在一个定义明确的气球模型上设计了新的实验 使用猪冠状动脉造成的过度伸展损伤。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的范围 通货膨胀及其对血管外膜纤维化和炎症的影响。 现在已经设计了四个具体目标来解决未得到回答的问题 这一领域的问题以及以前审查员的问题。 首先，申请者将确定外膜的贡献 肌成纤维细胞参与再狭窄的发生发展。其次，他将学习 缺血在刺激外膜炎症和纤维化中的作用。 申请人对缺血对ICAM的影响特别感兴趣 外膜表达IL-8。第三，假设 血管成形术导致外膜血流量减少，从而导致 将对缺血进行测试。最后，首席调查员将确定 血管成形术中血管外膜炎症的作用 损伤后血管壁的早期生长反应。