Mouse Model of Femoral Artery Denudation Injury Associated With the Rapid Accumulation of Adhesion Molecules on the Luminal Surface and Recruitment of Neutrophils

Abstract

Abstract-Techniques of arterial injury commonly used in animals to mimic endovascular procedures are not suitable for small mouse arteries. This has limited examination 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 femoral artery denudation by passage of an angioplasty guidewire. Intimal hyperplasia 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 1.1Ϯ0.1 at 4 weeks. No intimal proliferation was found in control sham-operated arteries. One hour after injury, the denuded surface was covered with platelets and leukocytes, predominantly neutrophils. This was associated with the accumulation of P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Expression of these adhesion molecules was not seen in the underlying medial smooth muscle cells. At 24 hours, few neutrophils remained on the denuded surface. At 1 week, macrophages and platelets were present in the vessel wall, partially covered by regenerated endothelium. Transluminal wire injury to the mouse femoral artery induces abundant intimal hyperplasia formation by 2 and 4 weeks and elicits the rapid accumulation of leukocytes and adhesion molecules on the denuded luminal surface. This model will be a valuable tool to study arterial injury in genetically modified mouse models.

Lysyl oxidase propeptide inhibits smooth muscle cell signaling and proliferation

“…Eleven week-old mice were subjected to guidewire-induced femoral artery injury or sham surgery [11,25]. After 14 days, animals were sacrificed, femoral arteries were fixed and embedded in paraffin [11].…”

“…LOX-PP epitopes occur at elevated levels in guidewire-injured femoral arteries. Eleven weekold mice were subjected to guidewire-induced femoral artery injury or sham surgery as described [11,25] and sacrificed after 14 days. Sections were subjected to immunohistochemistry with anti-LOX-PP antibody.…”

Increased In-Stent Stenosis in ApoE Knockout Mice

“…5 Mouse models also provide refinements in laboratory animal use, are cost-effective, and have a favorable generation time for cross-breeding experiments. Although mouse models would provide powerful approaches to investigate molecular mechanisms relevant to angioplasty and stenting, technical challenges have restricted such studies in mice to surrogate models of vascular injury, such as wire-denudation of endothelium 6,7 or perivascular polyethylene cuff placement. 8 These models have significant limitations in their ability to address potentially important aspects of balloon angioplasty and stenting.…”

“…5 The harvested stented vessel is grafted by sleeving the ends over the artery cuffs and securing them with 8-0 silk sutures. 6 The hemostatic clamps are removed and vigorous pulsations are seen within the stent graft. B, OCT imaging of stented vessel and 3D reconstruction demonstrating morphometric changes from carotid artery through to stented aortic graft.…”

Effect of p27 Deficiency and Rapamycin on Intimal Hyperplasia: In Vivo and In Vitro Studies Using a p27 Knockout Mouse Model

“…The femoral artery was exposed through a groin incision under a surgical microscope (Carl Zeiss, Thornwood, New York). Transluminal arterial injury was achieved by three passages of a 0.25-mm diameter angioplasty guidewire (Advanced Cardiovascular Systems, Tamecula, California) (Reis et al, 1998;Roque et al, 2000). After clamping the femoral vessels at the level of the inguinal ligament, an arteriotomy was made distal to the inferior epigastric artery, the guidewire inserted, the clamp removed, and the wire advanced to the level of the aortic bifurcation and pulled back.…”