Biphasic response of tropoelastin at the poststenotic dilation segment of the rabbit aorta.
Biphasic response of tropoelastin at the poststenotic dilation segment of the rabbit aorta.
复制标题
兔主动脉狭窄后扩张段原弹性蛋白的双相反应。
DOI：
10.1067/mva.2002.125017
复制
发表时间：
2002
影响因子：
4.3
通讯作者：
Glagov,Seymour
中科院分区：
文献类型：
--
作者：
Xu,Chengpei;Zarins,ChristopherK;Glagov,Seymour
目的探讨兔主动脉狭窄后扩张段原弹性蛋白基因表达的时程变化。实验时间点分别为缩窄后1、3、7天和2、4、8周(n=3)。其他动物(n=6)接受高胆固醇血症，以分析内膜病变中原弹性蛋白的表达。Northern和Western印迹分析原弹性蛋白信使RNA(MRNA)和蛋白的表达，免疫组织化学方法分析原弹性蛋白的分布。PSD节段的mRNA水平在第1天和第3天下降，随后在第2周和第4周上升(与对照组相比P<；0.05)。原弹性蛋白mRNA的这种双相变化与在2周和4周时原弹性蛋白水平的增加有关(与对照组相比P<；0.05)。PSD直径在4周时达到最大值，此后无明显增大。PSD组的内侧弹性板数略有减少，但中层厚度无明显变化。在高血压合并高胆固醇血症的动物中，PSD节段的内膜损害比近段的小得多。此外，原弹性蛋白蛋白不仅分布于PSD的内膜中，还分布于PSD的中层。结论PSD形成之前，原弹性蛋白基因的表达呈双相调控。原弹性蛋白在中膜中的不同分布提示原弹性蛋白在狭窄后适应反应中发挥作用，这可能为PSD壁提供更多的弹性。(《血管外科杂志》2002；36：605-12。)
ObjectiveThe purpose of this study was to assess the time course of tropoelastin gene expression in the poststenotic dilatation segment of rabbit aorta with experimental coarctation.MethodsMidthoracic aortic coarctation was created in rabbits to produce a PSD. The time points of the study after coarctation were 1, 3, and 7 days and 2, 4, and 8 weeks (n = 3 each). Additional animals (n = 6) were subjected to hypercholesterolemia for analysis of tropoelastin expression in intimal lesions. Northern and Western blot analyses were used to quantitate tropoelastin messenger RNA (mRNA) and protein, and immunohistochemistry was used to analyze tropoelastin distribution.ResultsThoracic aortic coarctation produced a moderate stenosis, which resulted in PSD. mRNA levels in the PSD segment decreased at days 1 and 3, followed by an increase at 2 and 4 weeks (P < .05 versus controls). This biphasic change in tropoelastin mRNA was associated with increase in tropoelastin protein levels at 2 and 4 weeks (P < .05 versus controls). PSD diameter reached a maximum at 4 weeks and did not increase significantly thereafter. The number of medial elastic laminae in PSD was reduced slightly, but media thickness was unchanged. Intimal lesions were much smaller in the PSD segment than in the proximal segment in animals with hypertension superimposed with hypercholesterolemia. Moreover, tropoelastin protein distributed not only in the intima but also in the media of the PSD.ConclusionTropoelastin gene expression is regulated in a biphasic pattern and precedes PSD formation. The differential distribution of tropoelastin in the media suggests a role for tropoelastin in the poststenotic adaptation response, which may provide increased elasticity to the PSD wall. (J Vasc Surg 2002;36:605-12.)