Aortic stiffness and aerobic exercise: Mechanistic insight from microarray analyses
Aortic stiffness and aerobic exercise: Mechanistic insight from microarray analyses
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DOI：
10.1249/01.mss.0000175052.37087.f8
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发表时间：
2005-10-01
期刊：
影响因子：
--
通讯作者：
Tanaka, H
中科院分区：
文献类型：
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作者：
Maeda, S;Iemitsu, M;Tanaka, H
引言/目的：定期有氧运动可降低主动脉僵硬度。然而，慢性运动降低动脉硬度的机制尚不清楚。为了确定这些变化的分子机制，用基因芯片技术检测了有氧运动训练对主动脉基因表达的影响。方法/结果：采用基因芯片技术比较安静对照组（8周龄）和运动训练组（8周龄，跑台运动4 wk）大鼠腹主动脉3800个基因表达水平的差异。运动组主动脉脉搏波传导速度（PWV）低于对照组，体动脉顺应性高于对照组（均P < 0.05）。在显示差异表达的323个基因中（206个基因上调和117个基因下调），总共29个基因（24个上调和5个下调基因）被鉴定为可能参与血管舒张和动脉硬化的潜在候选基因。采用实时定量聚合酶链反应，我们证实了芯片分析的结果，前列腺素EP 2受体（PGE-EP 2 R），前列腺素EP 4受体（PGE-EP 4 R），C型利钠肽（CNP），和内皮型一氧化氮合酶（eNOS）基因的差异表达。此外，动脉硬度和这些因素的水平之间存在适度的相关性。Western blot分析进一步证实eNOS基因在蛋白水平的差异表达。结论：这些结果表明，运动训练诱导改变表达的几个基因，包括前列腺素，CNP，和一氧化氮在主动脉和这些分子的变化（特别是eNOS的蛋白质表达改变）可能有助于，至少部分，运动训练对主动脉僵硬的有益影响。
Introduction/Purpose: Regular aerobic exercise reduces aortic stiffness. However, the mechanisms by which chronic exercise lowers arterial stiffness are not known. To determine the molecular mechanisms of these changes, the alteration of gene expression in the aorta by aerobic exercise training was measured with the microarray technique. Methods/Results: The differences in expression levels of 3800 genes in the abdominal aorta of sedentary control rats (8 wk old) and exercise-trained rats (8 wk old, treadmill running for 4 wk) were compared by the microarray analysis. Aortic pulse wave velocity (PWV) was lower and systemic arterial compliance was higher (both P < 0.05) in the exercise-trained group than in the control group. Of the 323 genes that displayed differential expression (upregulation of 206 genes and downregulation of 117 genes), a total of 29 genes (24 upregulated and 5 downregulated genes) were identified as potential candidate genes that may be involved in vasodilation and arterial destiffening. Using real-time quantitative polymerase chain reaction, we confirmed the results of microarray analysis that prostaglandin EP2 receptor (PGE-EP2R), prostaglandin EP4 receptor (PGE-EP4R), C-type natriuretic peptide (CNP), and endothelial nitric oxide synthase (eNOS) genes were differentially expressed. Furthermore, there were modest correlations between arterial stiffness and levels of these factors. Differential expression of eNOS gene was further verified at protein level by using Western blot analysis. Conclusion: These results suggest that exercise training induces the altered expression in several genes including prostaglandin, CNP, and nitric oxide in the aorta and that these molecular changes (particularly eNOS as its protein expression was altered) may contribute, at least in part, to the beneficial effect of exercise training on aortic stiffness.