Vein Graft Disease In A Knockout Mouse Model Of Hyperhomocysteinaemia

A major reason for vein graft failure after coronary artery bypass grafting is neointimal hyperplasia and thrombosis. Elevated serum levels of homocysteine (Hcy) are associated with higher incidence of cardiovascular disease, but homocysteine levels also tend to increase during the first weeks or months after cardiac surgery. To investigate this further, C57BL/6J mice (WT) and cystathionine-beta-synthase heterozygous knockout mice (CBS+/-), a mouse model for hyperhomocysteinaemia, underwent interposition of the vena cava of donor mice into the carotid artery of recipient mice. Two experimental groups were examined: 20 mice of each group underwent bypass surgery (group 1: WT donor and WT recipient; group 2: CBS+/- donor and CBS+/- recipient). After 4 weeks, the veins were harvested, dehydrated, paraffin-embedded, stained and analysed by histomorphology and immunohistochemistry. Additionally, serum Hcy levels in CBS knockout animals and in WT animals before and after bypass surgery were measured. At 4 weeks postoperatively, group 2 mice showed a higher percentage of thrombosis compared to controls, a threefold increase in neointima formation, higher general vascularization, a lower percentage of elastic fibres with shortage and fragmentation in the neointima, a lower percentage of acid mucopolysaccharides in the neointima and a more intense fibrosis in the neointima and media. In conclusion, hyperhomocysteinaemic cystathionine-beta-synthase knockout mice can play an important role in the study of mechanisms of vein graft failure. But further in vitro and in vivo studies are necessary to answer the question whether or not homocysteine itself or a related metabolic factor is the key aetiologic agent for accelerated vein graft disease.