Mouse model of femoral artery denudation injury associated with the rapid accumulation of adhesion molecules on the luminal surface and recruitment of neutrophils

Techniques of arterial injury commonly used in animals to mimic endovascula r procedures are not suitable for small mouse arteries. This has limited ex amination of the response to arterial injury in genetically modified mice. We therefore sought to develop a model of transluminal injury to the mouse femoral artery that would be reproducible and result in substantial levels of intimal hyperplasia. Mice of the C57BL/6 strain underwent bilateral femo ral artery denudation by passage of an angioplasty guidewire. Intimal hyper plasia was observed in 10% of injured arteries at 1 week, in 88% at 2 weeks , and in 90% at 4 weeks. The mean intimal-to-medial area ratio reached 1.1/-0.1 at 4 weeks. No intimal proliferation was found in control sham-operat ed arteries. One hour after injury, the denuded surface was covered with pl atelets and leukocytes, predominantly neutrophils. This was associated with the accumulation of P-selectin, intercellular adhesion molecule-1, and vas cular cell adhesion molecule-1. Expression of these adhesion molecules was not seen in the underlying medial smooth muscle cells. At 24 hours, few neu trophils remained on the denuded surface. At 1 week, macrophages and platel ets were present in the vessel wall, partially covered by regenerated endot helium. Transluminal wire injury to the mouse femoral artery induces abunda nt intimal hyperplasia formation by 2 and 4 weeks and elicits the rapid acc umulation of leukocytes and adhesion molecules on the denuded luminal surfa ce. This model will be a valuable tool to study arterial injury in genetica lly modified mouse models.