title: Upregulation of heat shock transcription factor 1 plays a critical role in adaptive cardiac hypertrophy.
abstract: 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.
authors.affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Minamino
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Toko
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kayama
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Masanori
authors.initials: M
authors.lastname: Sano
authors.forename: Eiichi
authors.initials: E
authors.lastname: Takaki
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Aoyagi
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tojo
authors.forename: Naoko
authors.initials: N
authors.lastname: Tajima
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001012:Aorta, Abdominal; D001794:Blood Pressure; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D015870:Gene Expression; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D000076249:Heat Shock Transcription Factors; D008026:Ligation; D008297:Male; D009206:Myocardium / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D005082:Physical Exertion; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D014157:Transcription Factors