Gene expression profiling of exercise-induced cardiac hypertrophy in rats.
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)-3beta, 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-3beta decreased significantly and those of Cain and ET-1 increased significantly with exercise training. Furthermore, LV mass index was significantly correlated with GSK-3beta 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-3beta, Cain, and ET-1) and that other genes (e.g. BNP, ACE) may differentiate physiological from pathological LV hypertrophy.[1]References
- Gene expression profiling of exercise-induced cardiac hypertrophy in rats. Iemitsu, M., Maeda, S., Miyauchi, T., Matsuda, M., Tanaka, H. Acta Physiol. Scand. (2005) [Pubmed]
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