Role of the mTOR Signalling Pathway in Experimental Rabbit Vein Grafts
Role of the mTOR Signalling Pathway in Experimental Rabbit Vein Grafts
复制标题
mTOR 信号通路在实验性兔静脉移植物中的作用。
DOI：
10.1016/j.hlc.2016.03.009
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发表时间：
2016-11-01
影响因子：
2.6
通讯作者：
Liu, Jichun
中科院分区：
文献类型：
--
作者：
Wang, Qun;Wan, Li;Liu, Jichun
背景冠状动脉旁路移植术用于治疗多支血管病变。研究表明，持续的适应不良重塑加速动脉粥样硬化，过度重塑导致移植物再狭窄。然而，很少有研究集中在机械目标的雷帕霉素（mTOR）信号参与移植veines.Methods重塑过程中被随机分配到组进行静脉移植再狭窄或假手术。分别于术后1、3、7、14、28和90天取出旁路移植物，并将其分别置于T-1、T-2、T-3、T-4、T-5和T-6组。T-0组为对照组。分析包括血管厚度、电子显微镜数据、TUNEL染色和增殖相关基因增殖细胞核抗原（PCNA）的表达。我们选择特定的时间点的基因表达，然后观察mTOR signaling.Results的变化静脉移植的早期阶段（手术后1至3天）导致细胞凋亡和细胞外基质的降解。手术后7天，细胞开始增殖。mTOR复合物2（mTORC 2）及其下游底物蛋白激酶C的RICTOR表达在早期（T-1和T-3）增强，并在T-1中更高。mTORC 1的上游基因调控在T-1中降低，在T-3中增加。其下游基因eIF 4 b和4 E-BP也有类似的变化。结论移植后第1天mTORC 1及其上下游基因功能受到抑制，mTORC 2功能增强。术后1周，mTORC 1功能恢复并增强时，mTORC 2仍过表达。因此，mTORC 2在静脉动脉化中起主要作用。
Background Coronary artery bypass grafting is employed for the treatment of multiple-vessel lesions. Studies have shown that continued maladaptive remodelling expedites atherosclerosis and that excessive remodelling leads to graft restenosis. However, few studies have focussed on mechanistic target of rapamycin (mTOR) signalling involved during remodelling of transplanted veins.Methods Rabbits were randomly allocated to groups undergoing vein-graft restenosis or sham surgery. At 1, 3, 7, 14, 28 and 90 days after surgery, we removed bypassed grafts and placed them in groups named T-1, T-2, T-3, T-4, T-5 and T-6, respectively. Group T-0 denoted the control group. Analysis included vessel thickness, electron microscope data, TUNEL staining, and expression of the proliferation-associated gene proliferating cell nuclear antigen (PCNA). We chose specific time-points of gene expression, and then observed changes in the mTOR signalling.Results The early stage of vein grafting (one to three days after surgery) led to apoptosis and degradation of the extracellular matrix. Seven days after surgery, cells began to proliferate. RICTOR expression in mTOR complex 2 (mTORC2) and that of its downstream substrate protein kinase C was enhanced in the early stage (T-1 and T-3), and was higher in T-1. mTORC1's upstream gene regulation decreased in T-1 and increased in T-3. Its downstream genes eIF4b and 4E-BP showed similar changes. Expression of eIF4e and eIF4b increased, and led to an increase in protein composition.Conclusions After transplantation, mTORC1 function and its upstream and downstream genes were inhibited on the first day after grafting, but mTORC2 function was enhanced. One week after surgery, mTORC2 was still over-expressed when mTORC1 function had recovered and become enhanced. Hence, mTORC2 plays a major role in arterialisation of veins.