A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia

A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia
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DOI:
10.1006/jmcc.2000.1238
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发表时间:
2000-11-01
影响因子:
5
通讯作者:
Nagai, R
Nagai, R
中科院分区:
医学2区
文献类型:
--
作者:
Sata, M;Maejima, Y;Nagai, R

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转基因小鼠是一种强大的工具,可以用来确定特定分子在包括血管重塑在内的各种生物现象中的作用。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,但对它们的重复性和生理意义提出了许多问题。在这里,我们报告了一种新的小鼠血管损伤模型,类似于球囊血管成形术。通过动脉切开术,在股动脉的一个小肌支上插入一根直的弹簧丝。将金属丝放在原地一分钟,以剥离和扩张动脉。拔除钢丝后,结扎肌支,恢复股动脉血流。管腔扩大,中膜细胞迅速发生凋亡。外弹力层周长增大的同时,管腔逐渐变窄,由平滑肌细胞组成的新生内膜增生。4周时,在植入钢丝的区域可重复形成同心均匀的新生内膜病变。所有受检菌株(C57BL/6J、C3H/HeJ、BALB/c和129/SVI)均可引起类似的过度增殖。该模型可广泛应用于从基因水平研究血管成形术后再狭窄的分子机制。(C)2000年学术出版社。
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/SVi). This model may be widely used to study the molecular mechanism of postangioplasty restenosis at the genetic level. (C) 2000 Academic Press.