© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Increased preload directly induces the activation of heat shock transcription factor 1 in the left ventricular overloaded heart
aDepartment of Cardiovascular Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan
bDepartment of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
cCREST (Core Research for Evolutional Science and Technology), JST (Japanese Science and Technology Cooperation), Japan
nishizaw{at}kcn.ne.jp
* Corresponding author. Current address: Department of Cardiovascular Surgery, Tenri Hospital, 200 Mishima, Tenri, Nara, 632-8552 Japan. Tel.: +81-743-635-611; fax: +81-743-625-576
Objectives: The rapid induction of heat shock proteins (HSPs) by cardiac overload has been shown using in vivo models and it is assumed that HSPs are involved in myocardial protection against cardiac overload. However, the mechanisms for the induction of heat shock response by cardiac overload remain unclear. We examined whether increased preload as mechanical stress directly induces heat shock gene expression. Methods: Rat hearts were isolated and perfused with Krebs–Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element. We examined the induction of the DNA-binding activity of heat shock transcription factor (HSF), by which the transcription of heat shock genes is mainly regulated, during increased preload of left ventricle (LV) or perfusion with the buffer containing epinephrine, norepinephrine, angiotensin II, or vasopressin. Results: In preloaded hearts, with LVEDP of both 30 and 50 mmHg, the DNA-binding activity of HSF1 was detected at 10 min, and increased at 20 and 60 min. At any time point, the activity with LVEDP of 50 mmHg was stronger than that with LVEDP of 30 mmHg. However, none of these hypertensive agents activated the DNA-binding activities of HSF. In afterloaded hearts, with the perfusion of norepinephrine, the activation of HSF was not induced. Conclusion: Our findings demonstrate that increased preload as mechanical stress directly induces the activation of HSF1 in the LV-overloaded heart.
KEYWORDS Gene expression; Mechanotransduction; Sequence (DNA/RNA/prot); Ventricular function
1 Current address: Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Ube, Japan.
2 Current address: Department of Cardiovascular Surgery, Kokura Memorial Hospital, Kitakyushu, Japan.
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