A MODEL OF ARTERIAL SMOOTH MUSCLE CELL PROLIFERATION TO STUDY RESTENOSIS

用于研究再狭窄的动脉平滑肌细胞增殖模型

• 批准号: 3879071
• 负责人: ELLIS UNGER
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3879071
• 关键词: artery stenosis; atherosclerosis; cell growth regulation; disease /disorder model; histopathology; intraluminal angioplasty; laboratory rabbit; protein engineering; vascular smooth muscle

Percutaneous transluminal coronary angioplasty (PTCA) has become a routine mode of therapy to relive arterial luminal stenosis in patients with coronary artery disease. Other trans-catheter interventional techniques, such as laser devices, mechanical atherectomy, and endovascular stents are currently being used in human patients. The "Achilles heel" of all interventional intravascular techniques is the phenomenon of arterial restenosis that occurs within 3 months after the PTCA in about 30% of the patients. It is likely that damage to the vessel wall during the arterial stretch at the time of angioplasty causes smooth muscle cell proliferation and the subsequent development of restenosis. Thus, restenosis is a healing phenomenon resulting from arterial injury and is independent of the atherosclerotic process. Efforts to gain better understanding of this phenomenon have been confounded by the lack of an appropriate animal restenosis model. By applying localized mechanical pressure to a rabbit artery, disruption of the normal histological architecture of the arterial wall occurs. As a result, striking smooth muscle cell proliferation occurs in the media of the vessel; a histopathologic reaction similar to human restenosis. In a preliminary study, this phenomenon was highly reproducible (75%). We are now beginning a series of experiments in which we plan to selectively inhibit the process of smooth muscle proliferation with a variety of genetically engineered peptides and toxins. Endpoints of the studies will relate to the degree of smooth muscle cell proliferation and extent of narrowing of the vessel lumen.

经皮冠状动脉腔内成形术(PTCA)已成为一种常规 动脉腔内狭窄缓解的治疗模式 冠状动脉疾病。其他经导管介入技术， 例如激光设备、机械动脉粥样硬化切除术和血管内支架 目前正用于人类患者。所有人的“阿喀琉斯之踵” 介入性血管内技术是动脉插管的现象 约30%的患者PTCA术后3个月内发生再狭窄 病人。很可能在动脉插管过程中对血管壁的损伤 血管成形术时的拉伸导致平滑肌细胞增殖 以及随后发生的再狭窄。因此，再狭窄是一种治愈。 动脉损伤引起的现象，与动脉损伤无关 动脉粥样硬化过程。 为更好地了解这一现象所做的努力 由于缺乏合适的动物再狭窄模型而感到困惑。通过 对兔动脉施加局部机械压力，使其破裂 动脉壁的正常组织结构可见。作为一名 结果：培养上清液中可见显著的平滑肌细胞增殖。 血管；类似于人类再狭窄的组织病理学反应。在一个 初步研究表明，这种现象具有很高的重复性(75%)。 我们现在正在开始一系列实验，我们计划在这些实验中 选择性地抑制平滑肌的增殖过程 各种基因工程多肽和毒素。的终结点 研究将涉及到平滑肌细胞的增殖程度和 血管管腔狭窄的程度。