Gene expression profiling of exercise-induced cardiac hypertrophy in rats.
OBJECTIVE
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).


METHODS
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.


CONCLUSIONS
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.
Iemitsu
M
M
Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Maeda
S
S
Miyauchi
T
T
Matsuda
M
M
Tanaka
H
H
D000222:Adaptation, Physiological; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D006332:Cardiomegaly / Q000235:genetics*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics; D019332:Endothelin-1 / Q000032:analysis / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D038362:Glycogen Synthase Kinase 3 / Q000032:analysis / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006352:Heart Ventricles; D007124:Immunoenzyme Techniques; D008297:Male; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051017:Apoptosis Regulatory Proteins; C113573:Cabin1 protein, rat; D002352:Carrier Proteins; D019332:Endothelin-1; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3