Abstract 2322: Graft Pretreatment With Green Tea Polyphenol, Epigallocatechin-3-gallate, Inhibits Neo-intimal Hyperplasia by Inactivating Mitogen-activated Protein Kinases in a Rabbit Vein Graft Model
Background: Development of neo-intimal hyperplasia (NIH) is considered to be one of the most responsible mechanisms for vein graft failure following coronary artery bypass grafting (CABG). Activation of mitogen-activated protein kinase (MAPK) is known to be crucial for the cellular proliferation and migration of smooth muscle cells in NIH. Epigallocatechin-3-gallate (EGCg), a green tea polyphenol, is known to be a natural antioxidant, which exhibits antiproliferative properties. We hypothesized that the graft pretreatment with EGCg could Inhibit NIH formation in the grafted vein by inactivating MAPKs.
Methods: We interposed a carotid artery by using the reversed ipsilateral external jugular vein in adult rabbits. Animals were divided into two groups according to the two different pretreatments (n=8 in each group). An external jugular vein were harvested from individual rabbits and immersed in saline or 1.0 mg/ml of EGCg in a saline solution at room temperature for one hour prior to grafting. At three weeks after grafting, NIH formation was histologically examined. At 1, 3 and 24 hours, and 7days after grafting, vein grafts were harvested to evaluate MAPK activation by western blot analysis (n=6 in each time-point).
Results: NIH was significantly suppressed in the EGCG-treated group compared with the control group. The intimal thickness in the control group and EGCG-treated group was 104.7±21.5 and 43.5±10.4 μm, (p<0.01), respectively. Neo-intima/media ratio for the corresponding groups was 0.76±0.23 and 0.47±0.32, (p<0.01). The population of Ki67-positive smooth muscle cells was significantly less in the EGCg-treated groups than the control group; 25.4±11.4 and 51.8±15.2% (p<0.01), respectively. Western blot analysis demonstrated that ERK1/2 and p38 expressions in the early phase of grafting were significantly down-regulated in the EGCg-treated groups compared wiith the control group.
Conclusion: Graft pretreatment with EGCg inhibited neo-intimal hyperplasia in a rabbit vein graft model by inactivating MAPKs. The method may offer a new simple but effective therapeutic alternative to prevent the neo-intimal hyperplastic response and subsequent vein graft failure following CABG.