Apoptosis and proliferation expression in autogenous vein grafts of low shear stress in a canine model

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12470266
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: HOKKAIDO UNIVERSITY
• Principal Investigator: YASUDA Keishu Hokkaido Univ., Grad. School of Med., Prof, 大学院・医学研究科, 教授 (60125359)
• Co-Investigator(Kenkyū-buntansha): NISHIBE Toshiya Hokkaido Univ., Med Hosp. Inst. ,, 医学部附属病院, 助手 (10261306)
• Project Period (FY): 2000 – 2002
• Keywords: Shear stress / autogenous vein graft / intimal / medial thickening / dog

Research Abstract

Objective : To evaluate the effect of low wall shear stress (t) in the expression of apoptosis and the proliferation ratio of intimal/medial layer of the arterially transplanted autogenous vein grafts in dogs. Material and Methods : A reversed autogenous femoral vein was implanted in the femoral artery of 8 beagle dogs. Four vein grafts were implanted under normal runoff conditions (control group), and another four vein grafts were implanted under conditions of poor runoff with low t(poor runoff group). Grafts were explanted four weeks later and analyzed by light microscopy and immunohistochemistry (Ki-67 and terminal transferase-mediated dUTP nick end labeling [TUNEL] methods). Results : Mean blood flow and t at implantation in the control group were 26.25^^+__-3.7 mL/min and 74.87 ^^+__-10.7 dyne/cm^2, respectively, whereas mean blood flow and t in the poor runoff group decreased significantly to 11.25 ^^+__-2.8 mL/min and 32.08^^+__-8.1 dyne/cm^2, respectively(p < 0.05). The intimal/medial thickness at four weeks after graft implantation in the poor runoff group was significantly more hyperplastic than the control group(489.96^^+__-5.9 vs 331.7^^+__-8.3mm ; p < 0.0001). Expression of Ki-67 showed a significantly higher level of cell cycling in grafts exposed to low t than in the normal t (3.0^^+__-0.4 vs 1.5^^+__-0.3 % ; p < 0.05). Apoptosis ratios were also significantly higher in the grafts exposed to low t (0.53^^+__-0.1 vs 0.21^^+__-0.04 %; p < 0.05). Conclusion : Vein grafts exposed to low t stimulated high rates of SMC proliferation and apoptosis, inducing persistent progression of intimal/medial thickness.