A MODEL OF ARTERIAL SMOOTH MUSCLE CELL PROLIFERATION TO STUDY RESTENOSIS

经皮冠状动脉腔内成形术（PTCA）已成为常规 动脉狭窄的治疗模式 冠心病其他经导管介入技术， 例如激光装置、机械动脉粥样硬化切除术和血管内支架， 目前用于人类患者。所有人的"致命弱点" 血管内介入技术是指 约30%的患者在PTCA后3个月内发生再狭窄。 患者很可能在动脉栓塞过程中对血管壁的损伤 血管成形术时的牵拉导致平滑肌细胞增殖 以及随后再狭窄的发展。因此，再狭窄是一种愈合 这种现象是由动脉损伤引起的，与动脉损伤无关。 动脉粥样硬化过程 为了更好地了解这一现象， 由于缺乏适当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， 出现动脉壁的正常组织结构。作为 结果，平滑肌细胞增殖发生在培养基中， 血管;类似于人类再狭窄的组织病理学反应。中 初步研究表明，这种现象具有很高的重现性（75%）。 我们现在开始了一系列的实验， 选择性抑制平滑肌增殖的过程， 各种基因工程肽和毒素。的端点 研究将涉及平滑肌细胞增殖的程度， 血管腔狭窄的程度。

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.