Published online before print November 9, 2006, doi: 10.1161/01.RES.0000252345.80198.97
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Submitted on March 31, 2006
Revised on October 28, 2006
Accepted on October 31, 2006
Upregulation of Heat Shock Transcription Factor 1 Plays a Critical Role in Adaptive Cardiac Hypertrophy
Masaya Sakamoto ;
From the Department of Cardiovascular Science and Medicine (M. Sakamoto, T.M., H.T., Y.K., Y.Z., M. Sano, I.K.), Chiba University Graduate School of Medicine; Department of Biochemistry and Molecular Biology (E.T., A.N.), Yamaguchi University Graduate School of Medicine, Ube; Japan Red Cross Medical Center (T.A.), Tokyo; Division of Diabetes, Metabolism and Endocrinology (M. Sakamoto, K.T., N.T.), Department of Internal Medicine, Jikei University School of Medicine, Tokyo; and Genome Science Division (H.A.), Research Center for Advanced Science and Technology, University of Tokyo, Japan.
* To whom correspondence should be addressed. E-mail: komuro-tky{at}umin.ac.jp.
Exercise-induced cardiac hypertrophy has been reported to have better prognosis than pressure overload-induced cardiac hypertrophy. Cardiac hypertrophy induced by exercise was associated with less cardiac fibrosis and better systolic function, suggesting that the adaptive mechanisms may exist in exercise-induced hypertrophy. Here, we showed a critical role of heat shock transcription factor 1 (HSF1), an important transcription factor for heat shock proteins, in the adaptive mechanism of cardiac hypertrophy. We examined expression of 8800 genes in the heart of exercise-induced hypertrophy model using DNA chip technique and compared with pressure overload-induced hypertrophy. Expression of HSF1 and its target molecule heat shock proteins was significantly upregulated in the heart by exercise but not by chronic pressure overload. Constitutive activation of HSF1 in the heart significantly ameliorated death of cardiomyocytes and cardiac fibrosis and thereby prevented cardiac dysfunction as well as hypertrophy induced by chronic pressure overload. Conversely, decreased activity of HSF1 in the heart promoted cardiac dysfunction in response to exercise, a load that normally leads to adaptive hypertrophy with preserved systolic function. Likewise, cardiac function was significantly impaired from the early phase of pressure overload, when HSF1 activation was inhibited. These results suggest that HSF1 plays a critical role in the transition between adaptive and maladaptive hypertrophy.
Key words: pressure overload • exercise • heart failure
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