Molecular mechanisms underlying exercise training-induced reduction of aortic stiffness

运动训练引起主动脉僵硬度降低的分子机制

基本信息

批准号：
16500391
负责人：
MAEDA Seiji
金额：
$ 2.37万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16500391/
关键词：
aorta exercise training mRNA vasoactive factor arterial stiffness heart プロスタグランディン CNP eNOS マイクロアレイ遺伝子

项目摘要

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. The differences in expression levels of 3,800 genes in the abdominal aorta of sedentary control (8 weeks old) and exercise-trained rats (8 weeks old, treadmill running for 4 weeks) 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 PCR, 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. 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.

定期有氧运动可以减少主动脉僵硬度。然而，长期运动降低动脉僵硬度的机制尚不清楚。为了确定这些变化的分子机制，利用微阵列技术测量了有氧运动训练对主动脉基因表达的改变。通过微阵列分析比较久坐对照组（8周龄）和运动训练大鼠（8周龄，跑步机跑步4周）腹主动脉3,800个基因表达水平的差异。运动训练组的主动脉脉搏波速度（PWV）低于对照组，全身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，117 个基因下调），共有 29 个基因（24 个上调基因和 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。使用实时定量PCR，我们确认了前列腺素EP2受体（PGE-EP2R）、前列腺素EP4受体（PGE-EP4R）、C型利钠肽（CNP）和内皮一氧化氮合酶（eNOS）的微阵列分析结果基因差异表达。此外，动脉僵硬度与这些因素的水平之间存在适度的相关性。通过Western blot分析进一步在蛋白质水平验证了eNOS基因的差异表达。这些结果表明，运动训练会引起主动脉中前列腺素、CNP 和一氧化氮等多个基因表达的改变，并且这些分子变化（特别是 eNOS，因为其蛋白质表达发生改变）可能至少部分有助于有益的健康。运动训练对主动脉僵硬度的影响。