Expression and Significance of Early Growth Response Gene-1 in Autogenous Vein Graft in Rats

Objective To investigate the development and significance of the expression of early growth response gene-1 (EGR-1) in autogenous vein graft in rats and detect the role of it in intimal hyperplasia. Methods Autogenous vein graft model was established in 90 Wistar rats, transplanting the right jugular vein to infra renal abdominal aorta by microsurgical technique. The vein graft samples were harvested at hour 1, 2, 6 and 24, day 3, 7,14, 28 and 42 after procedure. Normal vein as control group. Egr-1 mRNA was measured by reverse transcription-PCR and in situ hybridization. Western blot and immunohistochemistry were used to detect the protein expression of Egr-1. Results Intimal hyperplasia reached peak at day 28 after autogenous vein graft surgery. Egr-1 mRNA and Egr-1 protein hadn’t been found in the normal vein. The expressions of Egr-1 mRNA and Egr-1 protein had biphasic changes. By reverse transcription-PCR and in situ hybridization, we found that the level of Egr-1 mRNA rose at 1 hour after graft, the expression of Egr-1 mRNA was (35±7). Decline at hour 6, 24 and day 3, the positive rates of Egr-1 mRNA were (8±2), (8±6) and (8±4) respectively. Reincrease at day 7, a peak at day 28, the positive rate of Egr-1 mRNA was (45±6) (compared with other phase, P0.01). At day 42, the expression of Egr-1 mRNA declined again. Immunohistochemical staining and Western blot revealed Egr-1 protein had expressed at hour 2 early phase, the expression of Egr-1 protein was (30±5), and until to hour 6. The level of Egr-1 protein was decrease at hour 24 and day 3, the positive rates were (7±3) and (7±8) respectively. A peak at day 28, the positive rate of Egr-1 protein was (40±9) (compared with other phase, P0.01). We found that immu-noreative Egr-1 located vascular smooth muscle cells (VSMCs) and monocytes/macrophages in tunica media at the early phase of day 7 and 14, and in neointimal and medial VSMCs at later phase of day 28. Egr-1 was also present in the endoluminal endothelial cells. Conclusion In autogenous vein graft, Egr-1 plays an important role in the proliferation of VSMCs. Egr-1 may become a new target for the prevention and therapy of intimal hyperplasia, stenosis and emphraxis after vein graft.