Effect of angiotensin1-7 on intimal hyperplasia in autogenous vein graft in rats

Abstract

Objective Angiotensin1-7 (Ang1-7) and ITS inhibitor A779 were used to study the effect of Ang1-7 on intimal hyperplasia in autogenous vein graft. Methods The transplantation models of the external jugular vein to the abdominal aorta were established in 40 Specific Pathogen Free SD male rats. All models were randomly divided into control group, gel group, Ang1-7 group and A779 group (10 rats each). The adventitia of the transplanted veins was evenly sprayed with normal saline, Poloxamer 407, Poloxamer 407 mixed with Ang 1-7, Poloxamer 407 mixed with A779 respectively in each group forementioned. 5 rats form each group were sacrificed at 14th and 28th day respectively. The transplanted vein was intercepted and then stained with hematoxylin and eosin (HE). The thickness of the inner membrane (I) and medium membrane (M) of the vein grafts were measured by computer, and I/M ratio was calculated. The expression of proliferating cell nuclear antigen (PCNA), extracellular regulated protein kinase-1 (ERK-1) and angiotensin Ⅱ receptor 1 (AT1R) was determined by immunohistochemistry. Results (1)14th and 28th Day, the intimal hyperplasia of vein graft in Ang1-7 group [(59.26±7.51), (62.50±5.91) μm] was lighter than that in the other groups(P=0.001, respectively). (2)14th Day, the I/M ratio of vein graft in Ang1-7 group (0.67±0.05) was lower compare to that in other groups (P=0.001, 0.006, 0.001). 28th Day, the I/M ratio of vein graft in Ang1-7 group (0.71±0.14) was lower than that in the other groups(P=0.001, respectively). (3)There was statistically differences in the intimal thickness of vein graft between A779 group and control group at 14th, 28th day(P=0.007, 0.001). (4)14th Day, the expression of PCNA in the Ang1-7 group (21.80±7.05) was lower than that in other groups (P=0.011, 0.016, 0.001). 28th Day, the PCNA expression in the Ang1-7 group (12.80±5.31) was lower than that in the other groups (P=0.001, 0.002, 0.001). (5)14th Day, the express of ERK1 in vein graft Ang1-7 group (57.00±5.79) was lower than that in other groups (P=0.002, 0.003, 0.001). 28th Day, the express of ERK1 in vein graft Ang1-7 group(50.20±8.79) was lower than that in other groups (P=0.024, 0.017, 0.001). (6)14th Day, the express of AT1R in vein graft Ang1-7 group (27.20±6.87) was lower than that in other groups (P=0.001, 0.003, 0.001). 28th Day, the express of PCNA in vein graft Ang1-7 group(20.60±4.83) was lower than that in other groups (P=0.001, respectively). Conclusion The main cells resulting in intimal hyperplasia may be derived from the proliferation and migration of vascular smooth muscle cells in the medium membrane. Ang1-7 can significantly inhibit the expression of AT1R in the bridging vein, reduce its role in promoting endometrial proliferation, thereby reduce the proliferation and migration of VSMCs. Ang1-7 can also inhibit the expression of ERK in the bridging vein after vein transplantation; RAS and MAPK signal systems are involved in the intimal hyperplasia of vein graft. Key words: Angiotensin1-7; Vein graft; Intimal hyperplasia; Renin angiotensin system