Neointimal hyperplasia rapidly reaches steady state in a novel murine vein graft model.
OBJECTIVE: Neointimal hyperplasia remains a principal cause of vein graft failure. Genetic contributions to vein graft neointimal hyperplasia could be well studied in the mouse; however, surgical approaches to vein bypass surgery in the mouse have yet to replicate approaches commonly employed in human patients. Consequently, the goal of this study was to develop a murine interposition vein graft model that reproduces characteristics of human vein graft disease. METHOD: Using C57BL/6J mice, we excised inferior venae cavae (IVCs) from donor mice and grafted them, with end-to-side anastomosis, into the carotid circulation of recipients. IVC grafts were harvested from 3 to 56 days postoperatively, and analyzed for the development of neointima and media. RESULTS: Thickening of both the vein graft neointima and media progressed rapidly between postoperative weeks 1 and 4, and reached steady state levels by approximately week four, with a graft-wall thickness of 91 +/- 4 microm (14 cell layers), a lumen area of 0.56 mm(2), an average neointima-media ratio of 0.4 to 0.6, and a predominance of alpha-smooth muscle actin-staining cells. Comprising predominately smooth muscle actin-expressing cells, the neointima was 50% thicker in the proximal than in the distal third of the grafts (P <.001), but proximal and distal vein graft anastomoses were widely patent. CONCLUSIONS: In syngeneic murine carotid interposition IVC grafts implanted with end-to-side anastomoses, moderate, nonocclusive neointimal hyperplasia reaches steady state after the fourth postoperative week. This neointimal hyperplasia, like that of human grafts, predominates near vein graft anastomoses. This vein graft model should facilitate genetic analyses of the pathogenesis of neointimal hyperplasia.
Zhang, L; Hagen, P-O; Kisslo, J; Peppel, K; Freedman, NJ
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