Sata M, Maejima Y, Adachi F, Fukino K, Saiura A, Sugiura S, Aoyagi T, Imai Y, Kurihara H, Kimura K, Omata M, Makuuchi M, Hirata Y, Nagai R
Department of Cardiovascular Medicine, University of Tokyo, Tokyo, 113-8655, Japan.
J Mol Cell Cardiol. 2000 Nov;32(11):2097-104. doi: 10.1006/jmcc.2000.1238.
Genetically modified mice serve as a powerful tool to determine the role of specific molecules in a wide variety of biological phenomena including vascular remodeling. Several models of arterial injury have been proposed to analyze transgenic/knock-out mice, but many questions have been raised about their reproducibility and physiological significance. Here, we report a new mouse model of vascular injury that resembles balloon-angioplasty. A straight spring wire was inserted into the femoral artery via arterioctomy in a small muscular branch. The wire was left in place for one minute to denude and dilate the artery. After the wire was removed, the muscular branch was tied off and the blood flow of the femoral artery was restored. The lumen was enlarged with rapid onset of medial cell apoptosis. While the circumference of the external elastic lamina remained enlarged, the lumen was gradually narrowed by neointimal hyperplasia composed of smooth muscle cells. At 4 weeks, a concentric and homogeneous neointimal lesion was formed reproducibly in the region where the wire had been inserted. Similar exuberant hyperplasia could be induced in all strains examined (C57BL/6J, C3H/HeJ, BALB/c, and 129/SVj). This model may be widely used to study the molecular mechanism of post-angioplasty restenosis at the genetic level.
转基因小鼠是确定特定分子在包括血管重塑在内的多种生物学现象中作用的有力工具。已经提出了几种动脉损伤模型来分析转基因/基因敲除小鼠，但关于它们的可重复性和生理意义也提出了许多问题。在此，我们报告一种类似于球囊血管成形术的新型血管损伤小鼠模型。通过在一个小肌肉分支处进行动脉切除术，将一根直的弹簧丝插入股动脉。将丝线留在原位一分钟以剥脱并扩张动脉。移除丝线后，结扎肌肉分支并恢复股动脉血流。随着中膜细胞迅速发生凋亡，管腔扩大。虽然外弹力膜的周长仍然扩大，但管腔逐渐被由平滑肌细胞组成的内膜增生所狭窄。在4周时，在插入丝线的区域可重复形成同心且均匀的内膜病变。在所检查的所有品系（C57BL/6J、C3H/HeJ、BALB/c和129/SVj）中均可诱导出类似的过度增生。该模型可广泛用于在基因水平研究血管成形术后再狭窄的分子机制。
