Ramirez J A, Sanchez L A, Marin M L, Lyon R T, Parsons R E, Suggs W D, Veith F J
The Division of Vascular Surgery, Department of Surgery, Montefiore Medical Center, New York, New York 10467, USA.
J Surg Res. 1996 Mar;61(2):323-9. doi: 10.1006/jsre.1996.0124.
The expression of c-MYC oncoprotein in proliferating smooth muscle cells (SMCs) was analyzed in an experimental model of vein graft intimal thickening.
Superficial epigastric vein grafts were inserted into the femoral arteries of male Sprague-Dawley rats. The vein grafts were harvested at 6 hr, 2 days, 1 week, 2 weeks, and 4 weeks after grafting and were rapidly frozen in liquid nitrogen. Immunohistochemical labeling and morphologic analysis of vein graft sections with a double staining technique were used to identify c-MYC/alpha SMC actin and proliferating cell nuclear antigen (PC10)/alpha SMC actin within intimal cells. c-MYC/alpha SMC actin and PC10/alpha SMC actin positive cells were quantitated in the perianastomotic area (R-1) and the body of the graft (R-2) for each time period. Total wall and intimal thickness of perfusion fixed vein grafts were measured with a computer digitized system.
Intimal and total wall thickening in the R-1 region peaked at 1 week (27.4 and 579.4 microns respectively) and were significantly thicker (P < 0.01) than the same region at 6 hr after graft implantation (6.0 and 113.5 microns respectively). Staining for c-MYC and PC10 in R-1 was also significantly higher (P < 0.05) at 1 week (5.75 and 7.00 positive cells/10 cells, respectively) compared with that at 6 hr (1.5 and 1.33, respectively). The R-1 region stabilized and remodeled over the following 3 weeks, while c-MYC and PC10 staining progressively decreased. In the R-2 region, intimal thickness significantly increased (P < 0.05) from 6 hr (4.0 micrometers) to 1 week (12.0 micrometers) and stabilized, while total wall thickness increased throughout the first week and the difference became significant at 2 weeks (P < 0.05). Staining for c-MYC and PC10 paralleled the staining in R-1 with a significant peak at 1 week (P < 0.05).
c-MYC oncoprotein is expressed early after experimental vein grafting, with peak expression at 1 week. This occurs during a period of maximal intimal thickening, SMC proliferation, and increased expression of PC10. Expression of c-myc protooncogene may contribute to the induction and regulation of SMC proliferation, producing intimal hyperplasia.
在静脉移植物内膜增厚的实验模型中分析增殖性平滑肌细胞（SMC）中c-MYC癌蛋白的表达。
将腹壁浅静脉移植物植入雄性Sprague-Dawley大鼠的股动脉。在移植后6小时、2天、1周、2周和4周采集静脉移植物，并迅速在液氮中冷冻。采用免疫组织化学标记和双重染色技术对静脉移植物切片进行形态学分析，以鉴定内膜细胞中的c-MYC/α-SMC肌动蛋白和增殖细胞核抗原（PC10）/α-SMC肌动蛋白。对每个时间段吻合口周围区域（R-1）和移植物主体（R-2）中的c-MYC/α-SMC肌动蛋白和PC10/α-SMC肌动蛋白阳性细胞进行定量。用计算机数字化系统测量灌注固定的静脉移植物的总壁厚度和内膜厚度。
R-1区域的内膜和总壁增厚在1周时达到峰值（分别为27.4微米和579.4微米），显著厚于移植后6小时时的同一区域（分别为6.0微米和113.5微米）（P<0.01）。R-1区域中c-MYC和PC10的染色在1周时（分别为5.75和7.00个阳性细胞/10个细胞）也显著高于6小时时（分别为1.5和1.33）（P<0.05）。在接下来的3周内，R-1区域稳定并重塑，而c-MYC和PC10染色逐渐减少。在R-2区域，内膜厚度从6小时时的4.0微米显著增加（P<0.05）至1周时的12.0微米并稳定下来，而总壁厚度在第一周内持续增加，在2周时差异变得显著（P<0.05）。c-MYC和PC10的染色与R-1区域的染色情况相似，在1周时出现显著峰值（P<0.05）。
c-MYC癌蛋白在实验性静脉移植后早期表达，在1周时表达达到峰值。这发生在内膜增厚、SMC增殖以及PC10表达增加的最大时期。c-myc原癌基因的表达可能有助于诱导和调节SMC增殖，从而产生内膜增生。
