Gene expression profiling of exercise-induced cardiac hypertrophy in rats
Gene expression profiling of exercise-induced cardiac hypertrophy in rats
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DOI：
10.1111/j.1365-201x.2005.01494.x
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发表时间：
2005-12-01
期刊：
影响因子：
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通讯作者：
Tanaka, H
中科院分区：
文献类型：
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作者：
Iemitsu, M;Maeda, S;Tanaka, H
目的：运动训练引起生理性心肌肥厚，在运动过程中增强心功能。然而，潜在的分子机制尚不清楚。我们研究了运动训练诱导的心肌肥厚的基因表达谱，使用从运动训练和久坐的大鼠（12周龄）中切除的左心室（LV）作为对照。方法：实验组大鼠在跑步机上运动8周。结果：运动训练组大鼠左心室质量指数和壁厚均显著大于对照组，表明训练大鼠出现心肌肥厚。在微阵列分析中分析的3800个基因中，共有75个相关基因（33个基因上调，42个基因下调）在运动训练中显示出改变。在这些基因中，我们重点研究了糖原合成酶激酶(GSK)-3 β、钙调磷酸酶抑制剂（Cain）和内皮素(ET)-1在病理心肌肥大中的作用，并利用定量PCR、Western blot和EIA分析在mRNA和蛋白/肽水平上证实了微阵列分析的结果。运动训练后GSK-3 β基因表达显著降低，Cain和ET-1基因表达显著升高。左室质量指数与GSK-3 β蛋白活性（r = -0.70, P < 0.01）和组织ET-1浓度（r = 0.52, P < 0.05）呈极显著相关。脑利钠肽（BNP）、血管紧张素纠正酶（ACE）、白细胞介素-6、血管细胞粘附分子(VCAM)-1基因表达无明显变化。结论：这些发现提示生理性和病理性左室肥厚可能在诱导左室肥厚的分子机制上是相同的（如GSK-3 β、Cain和ET-1），其他基因（如BNP、ACE）可能区分生理性和病理性左室肥厚。
Aims: Exercise training causes physiological cardiac hypertrophy, which acts to enhance cardiac function during exercise. However, the underlying molecular mechanisms are unclear. We investigated gene expression profile of exercise training-induced cardiac hypertrophy using left ventricle (LV) excised from exercise-trained and sedentary control rats (12-week old).Method: Rats in the training group exercised on a treadmill for 8-week.Results: Left ventricular mass index and wall thickness in the exercise-trained group were significantly greater than that in the control group, indicating that the trained rats developed cardiac hypertrophy. Of the 3800 genes analysed in the microarray analyses, a total of 75 relevant genes (upregulation of 33 genes and downregulation of 42 genes) displayed alterations with exercise training. Among these genes, we focused on glycogen synthase kinase (GSK)-3 beta, calcineurin-inhibitor (Cain), and endothelin (ET)-1 for their implicated roles in pathological cardiac hypertrophy, and confirmed the results of microarray analysis at mRNA and protein/peptide levels using quantitative PCR, Western blot, and EIA analyses. The gene expression of GSK-3 beta decreased significantly and those of Cain and ET-1 increased significantly with exercise training. Furthermore, LV mass index was significantly correlated with GSK-3 beta protein activity (r = -0.70, P < 0.01) and tissue ET-1 concentration (r = 0.52, P < 0.05). There were no changes in gene expressions in brain natriuretic peptide (BNP), angiotensin-correcting enzyme (ACE), interleukin-6, and vascular cell adhesion molecule (VCAM)-1.Conclusion: These findings suggest that physiological and pathological LV hypertrophy may share some of the same molecular mechanisms in inducing LV hypertrophy (e.g. GSK-3 beta, Cain, and ET-1) and that other genes (e.g. BNP, ACE) may differentiate physiological from pathological LV hypertrophy.