A mouse vein graft disease model

What is it about?

To demonstrate an advanced mouse interposition vein graft model that produces characteristic of human vein graft disease.

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Why is it important?

Autologous vein grafts are the most widely used conduits for cardiovascular and peripheral vascular surgical procedures to bypass arterial stenosis. Despite refinements in surgical technique, the rate of vein graft failure remains high: up to 30% of vein grafts become stenotic and require intervention within 2 years because hemodynamically significant neointimal hyperplasia develops. Neointimal hyperplasia is a process involving smooth muscle cell proliferation and migration into the intima as well as extracellular matrix synthesis. This vein graft neointimal hyperplasia is believed to form a nidus for accelerated atherosclerosis and consequent vein graft failure. Pathogenic factors important in the development of vein graft neointimal hyperplasia remain incompletely understood. To study the gene products important in vein graft neointimal hyperplasia, investigators have begun to use the mouse as an experimental system because of the wealth of targeted gene deletions or overexpression that have been created in mice. Previous murine vein graft neointimal hyperplasia studies have avoid end-to-side graft anastomoses by employing arterial cuffs that facilitated technically simple ligation of the vein graft to the transected artery. Thereby, these studies cannot assess the important contribution to vein graft pathology of neointimal hyperplasia at the sites of end-to-side anastomoses, where most clinical vein graft settings tend to fail first. To model human venous bypass surgery more faithfully in the mouse, we developed a carotid interposition vein graft model by using end-to-side anastomoses method in the C57BL/6J inbred mouse strain. In this study, we characterize the evolution of these vein grafts morphologically, to the point of steady state graft wall thickness.