The Role of Bone Morphogenic Protein-4 in the Progression of Vein Graft Hyperplastic Remodeling under

【Abstract】 Objective This study was designed to assess the vessel wall characteristics and the expression levels of bone morphogenic protein4(BMP4) and proliferating cell antigen Ki67 in vein grafts harvested from diabetic rats, and to investigate the role of BMP4 in progression of vein graft hyperplastic remodeling under hyperglycemic condition. Methods 48 male SpragueDawky rats 〔body mass (194±16) g〕 aged 8 weeks were randomly divided into diabetes mellitus (DM) group ( n=24) and nondiabetes mellitus (NDM) group ( n=24). The DM rats were induced by streptozotocin in combination with highsugar and highfat diet. The unilateral external jugular vein was interposition grafted into the common carotid arteries in the two groups. The vein grafts were harvested at preoperatively and 1, 2 and 4 weeks postoperatively ( n=6) in each group. The morphological characteristics of the venous graft wall were evaluated by hematoxylineosin staining, and the expression levels and the distribution of Ki67 and BMP4 were assessed by immunohistochemistry analysis, then the expression of BMP4 gene and protein was measured by realtime polymerase chain reaction (RTPCR) and Western blot assay respectively. Results In the progression of rats vein grafts hyperplastic remodeling, the venous wall thickness of rats thickened with time increasing, and the intimal and medial thickness of the vein grafts harvested from DM rats were significantly higher than those from NDM rats at the same time postoperatively ( P<0.05). Ki67 was highly xpressed in smooth muscle cells nucleus located in the rats vein grafts, and its expression level was upregulated