Mouse Model of Venous Bypass Graft Arteriosclerosis

Abstract

Autologous vein grafts remain the only surgical alternative for many types of vascular reconstruction, but the failure rate of these grafts after 1 year approaches 20%.

Rapid Development of Vein Graft Atheroma in ApoE-Deficient Mice

“…13 In our previous study, we established a new model for the study of neointima formation of venous bypass grafts in mice, and demonstrated the presence of abundant MAC-1-positive monocytes/macrophages and smooth muscle cells (SMCs) in the early stages of lesions in vein grafts. 14 In the present study, we developed and characterized an animal model of vein graft atheroma in apoE knockout mice, and demonstrated that hypercholesterolemia promotes the formation of typical atherosclerotic plaques, ie, atheroma in vein bypass grafts.…”

“…14 Figure 4 and Table 1 demonstrate the presence of abundant SMCs in venous bypass graft lesions 4 and 8 weeks after surgery. Initially, a monolayer of SMCs in normal vein walls stained strongly positive (data not shown), and no staining was seen in vein segments stained with normal rat serum as a negative control (Figure 4a).…”

“…14 Briefly, 3-month-old mice were anesthetized with pentobarbital sodium (50 mg/kg body weight, i.p.). The vena cava vein was harvested and washed with saline solution containing 100 U/ml of heparin.…”

“…14,15 Briefly, serial 5-m-thick frozen sections were overlaid with rat monoclonal antibodies against mouse MAC-1 leukocytes (CD11b/18), CD4, or CD8 (PharMingen, San Diego, CA). Sections were visualized with alkaline phosphatase-anti-alkaline phosphatase complex (Dakopatts, Copenhagen, Denmark) and developed using a substrate solution containing 9.8 ml Tris buffer (0.1 mol/L, pH 8.2), 0.2 ml dimethylformamide, 8 mg naphthol AS-MX phosphate, 3 mg levamisole, and 10 mg Fast Red TR salt (Sigma).…”

“…14 In apoEϪ/Ϫ mice, typical atheroma in 8-week vein grafts displayed the classical complex morphological features and heterogeneous cellular compositions. Atheromatous lesions consisted of the fibrous cap (Figure 3, b and c), infiltrated mononuclear cells (Figure 3b), foam cells (Figure 3c), cholesterol crystal structure (Figure 3d), necrotic core with calcification (Figure 3e), and neovasculature ( Figure 3f).…”