Xu Chengpei, Zarins Christopher K, Glagov Seymour
Department of Surgery, Stanford University, Division of Vascular Surgery, 300 Pasteur Drive, Suite H3600, Stanford, California, USA.
Exp Mol Pathol. 2002 Apr;72(2):115-23. doi: 10.1006/exmp.2002.2423.
To assess elastin biosynthesis in the aortic wall in response to acute elevation of blood pressure, we studied the aortic gene expression of tropoelastin in a rabbit midthoracic aortic coarctation model. The time points of the study were 1, 3, and 7 days and 2, 4, and 8 weeks after coarctation. Additional animals were subjected to hypercholesterolemia for analysis of tropoelastin expression in the intimal lesion. mRNA for tropoelastin was quantitated by Northern blot analysis and its distribution was revealed by in situ hybridization. The 65-kDa tropoelastin was analyzed by Western blotting and immunohistochemistry. Tropoelastin mRNA proximal to the coarctation was increased at 2 weeks and returned to baseline by 8 weeks (P < 0.05 versus control). Changes in 65-kDa tropoelastin corresponded to those of mRNA. Tropoelastin gene was expressed mainly in the intima and in the outer media at the proximal region to the stenoses, which was particularly remarkable in the intimal lesion. The results indicate that tropoelastin gene expression was enhanced in the early remodeling response to elevated blood pressure. The distribution of newly synthesized tropoelastin in the outer media suggests a reenforcement role of tropoelastin, which preserves mechanical resiliency in response to changes in tensile stress.
为了评估主动脉壁中弹性蛋白生物合成对血压急性升高的反应,我们在兔胸段主动脉缩窄模型中研究了原弹性蛋白的主动脉基因表达。研究的时间点为缩窄后1、3和7天以及2、4和8周。另外的动物接受高胆固醇血症处理,以分析内膜病变中原弹性蛋白的表达。通过Northern印迹分析对原弹性蛋白的mRNA进行定量,并通过原位杂交揭示其分布。通过蛋白质印迹法和免疫组织化学分析65-kDa原弹性蛋白。缩窄近端的原弹性蛋白mRNA在2周时增加,并在8周时恢复至基线水平(与对照组相比,P < 0.05)。65-kDa原弹性蛋白的变化与mRNA的变化一致。原弹性蛋白基因主要在内膜以及狭窄近端区域的外膜中表达,这在内膜病变中尤为明显。结果表明,在对血压升高的早期重塑反应中原弹性蛋白基因表达增强。新合成的原弹性蛋白在外膜中的分布表明原弹性蛋白具有强化作用,可在响应拉伸应力变化时保持机械弹性。