Increased neointimal formation after surgical vein grafting in a murine model of type 2 diabetes.

ABSTRACT

BACKGROUND: Diabetes is an independent risk factor for the development of neointimal hyperplasia and subsequent vein graft failure after coronary or peripheral artery bypass grafting. We evaluate a new mouse model of surgical vein grafting to investigate the mechanisms of neointimal formation in the setting of type 2 diabetes. METHODS AND RESULTS: Surgical vein grafts were created by inserting vein segments from age-matched C57BL/KsJ wild-type mice into the infra-renal aorta of lepr(db/db) diabetic and C57BL/KsJ wild-type mice. Mice were euthanized &4 weeks later, and vein grafts were analyzed using morphometric and immunohistochemical techniques. A significant increase in neointimal formation was noted in lepr(db/db) mice (139+/-64 versus 109+/-62 mm2; P=0.008) after 4 weeks. This difference was mainly secondary to an increase in collagen formation within the lesion in the vein grafts from lepr(db/db) mice (0.53+/-0.4 versus 0.44+/-0.05; P<0.001), whereas only slight increases (P=not significant) in alpha actin-stained smooth muscle cells were noted in the lepr(db/db) mice. CONCLUSIONS: We established a new physiologically relevant model of surgical vein grafting in mice. In this report, type 2 diabetes was associated with significant increase in extracellular matrix deposition in addition to increased smooth muscle cell deposition. This new model may allow mechanistic studies of cellular and molecular pathways of increased neointimal formation in the setting of diabetes.