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

Genetically modified mice serve as a powerful tool to determine the role of specific molecules in a wide variety of biological phenomena including vas cular remodeling. Several models of arterial injury have been proposed to a nalyze transgenic/knock-out mice, but many questions have been raised about : their reproducibility and physiological significance. Here, we report a n ew mouse model of vascular injury that resembles balloon-angioplasty. A str aight 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 denud e and dilate the artery. After the wire was removed, the muscular branch wa s 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 circumfe rence of the external elastic lamina remained enlarged, the lumen was gradu ally narrowed by neointimal hyperplasia composed of smooth muscle cells. At 4 weeks, a concentric and homogeneous neointimal lesion was formed reprodu cibly in the region where the wire had been inserted. Similar exuberant hyp erplasia 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 mecha nism of postangioplasty restenosis at the genetic level. (C) 2000 Academic Press.