Increased preload directly induces the activation of heat shock transcription factor 1 in the left ventricular overloaded heart.
OBJECTIVE
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.


CONCLUSIONS
Our findings demonstrate that increased preload as mechanical stress directly induces the activation of HSF1 in the LV-overloaded heart.
Department of Cardiovascular Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan. nishizaw@kcn.ne.jp
Junichiro
J
Nishizawa
Akira
A
Nakai
Masashi
M
Komeda
Toshihiko
T
Ban
Kazuhiro
K
Nagata
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000378:metabolism; D006439:Hemodynamics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000378:metabolism*
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C000619709:Hsf1 protein, rat; D014157:Transcription Factors; D014667:Vasopressins; D000804:Angiotensin II; D009638:Norepinephrine; D004837:Epinephrine