The Significance of Neuregulin-1/ErbB Expression in Autogenous Vein Grafts in a Diabetic Rat Model.

Abstract

Diabetes mellitus (DM) is an important risk factor for increased vein graft failure after bypass surgery. The neuregulin-1 (NRG-1)/ErbB signaling system plays a critical role in neointimal formation after vascular injury as well as the proliferation and migration of mitogen-induced vascular smooth muscle cells; however, changes in NRG-1/ErbB signaling leading to vein grafts attrition in DM remain largely unexplored. Therefore, the aim of this study was to investigate changes in NRG-1/ErbB signaling in vein grafts in diabetic rats. To do this, a rat model of DM was established by streptozotocin injection followed by engraftment of autologous jugular veins to carotid arteries to induce intimal hyperplasia. After vein graft harvest, a pathohistological examination was performed; changes in NRG-1 and ErbB expression were also assessed. NRG-1 and ErbB expression localized to endothelial cells and vascular smooth muscle cells, which is consistent with the arterialization of vein grafts. NRG-1, ErbB2, and ErbB4 expression significantly decreased in vein grafts over time. Our findings show that NRG-1/ErbB signaling is impaired in vein grafts of diabetic rats, suggesting an important role for this pathway in the pathogenesis of intimal hyperplastic lesions in vein grafts of patients with DM.