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

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.

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.

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). Ki-67 was highly xpressed in smooth muscle cells nucleus located in the rats vein grafts,and its expression level was up-regulated gradually in the progression of vein graft failure,and the Ki 67 positive cells of vein grafts from DM rats were significantly higher than those from NDM controls at the same period ( P<0.05). Immunohistochemistry analysis showed that BMP4 was expressed in smooth muscle cells cytoplasmof the rats vein grafts,combined with the results of RT-PCR and Western blot assay,there was a little BMP4 expression could be seen in venous wall of NDM rats,while BMP4 positive cells and the expression level of BMP4 gene and protein from DM rats vein grafts was increasing with obvious time dependence and significantly higher than the NDM rats ( P<0.05).

The morphological and pathological changes within the venous wall were significantly correlated with the high expression levels of BMP4 in vein grafts harvested from diabetic rats,implying a potential role of BMP4 in the progression of accelerated vein graft failure under hyperglycemic condition.