Chung Ada W Y, Wong Jerry, Luo Honglin, Hsiang York N, van Breemen Cornelis, Okon Elena B
James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, Canada.
Can J Cardiol. 2007 Dec;23(14):1147-54. doi: 10.1016/s0828-282x(07)70886-3.
Vein arterialization following bypass surgery often leads to graft occlusion, but the underlying cellular mechanisms have been poorly studied.
Cell cycle progression and the activation of proliferation signalling were compared in arterialized grafts prepared either according to the conventional procedure or using pharmacological relaxation with the native vein.
Using the porcine carotid-jugular bilateral interposition graft model on one side, a segment of porcine jugular vein was prepared for grafting using the conventional procedure, with pressure distention at 300 mmHg; the segment grafted on the other side was treated with a combination of pharmacological vasodilators. Both veins were grafted into the carotid artery for two weeks.
On the immunolabelling of proliferation cell nuclear antigen, a greater number of proliferating cells was found in the conventionally prepared grafts compared with pharmacologically prepared grafts. Cyclin D1 expression and phosphorylation of retinoblastoma increased after implantation, coinciding with nuclear accumulation of beta-catenin, activation of the Akt and mitogen-activated protein kinase cascades, and upregulated phosphatase and tensin homologue phosphorylation. Replacement of distention with pharmacological relaxation reduced the increase in cyclin D1 expression, phosphorylation of retinoblastoma, Akt-Thr(308), glycogen synthase kinase 3 beta and p38, but not extracellular signal-regulated kinases. This technique preserved the active phosphatase and tensin homologue, as well as the expression of cyclin-dependent kinase inhibitor p21(Cip1), while elevating the expression of p27(Kip1).
It was concluded that two-week arterial implantation stimulates proliferation signalling and promotes the cell cycle in vein grafts. Replacement of the conventional preparation procedures with pharmacological vasorelaxation restricts the activation of proliferation and cell cycle progression, and can be beneficial for improving vein graft patency.
旁路手术后静脉动脉化常导致移植物闭塞，但潜在的细胞机制研究较少。
比较按照传统方法制备的动脉化移植物与使用天然静脉药物松弛制备的动脉化移植物中的细胞周期进程和增殖信号激活情况。
在一侧使用猪颈动脉 - 颈静脉双侧间置移植物模型，采用传统方法在300 mmHg压力扩张下制备一段猪颈静脉用于移植；另一侧移植的静脉段用多种血管扩张药物联合处理。将两条静脉都移植到颈动脉中两周。
增殖细胞核抗原免疫标记显示，与药物处理制备的移植物相比，传统方法制备的移植物中有更多增殖细胞。植入后细胞周期蛋白D1表达和视网膜母细胞瘤磷酸化增加，同时伴有β - 连环蛋白核内积聚、Akt和丝裂原活化蛋白激酶级联激活以及磷酸酶和张力蛋白同源物磷酸化上调。用药物松弛替代扩张可减少细胞周期蛋白D1表达、视网膜母细胞瘤磷酸化、Akt - Thr(308)、糖原合酶激酶3β和p38的增加，但细胞外信号调节激酶不受影响。该技术保留了活性磷酸酶和张力蛋白同源物以及细胞周期蛋白依赖性激酶抑制剂p21(Cip1)的表达，同时提高了p27(Kip1)的表达。
得出结论，两周的动脉植入刺激增殖信号并促进静脉移植物中的细胞周期。用药物血管舒张替代传统制备程序可限制增殖激活和细胞周期进程，可能有利于改善静脉移植物通畅率。
