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

Objectives: The rapid induction of heat shockproteins (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 shockresponse by cardiac overload remain unclear. We examined whether increased preloadas mechanical stress directly induces heat shockgene expression. Methods: Rat hearts were isolated and perfused with Krebs–Henseleit bufferby the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shockelement. We examined the induction of the DNA-binding activity of heat shocktranscription factor (HSF), by which the transcription of heat shockgenes is mainly regulated, during increased preloadof left ventricle (LV) or perfusion with the buffer containing epinephrine, norepinephrine, angiotensin II, or vasopressin. Results: In preloadedhearts, with LVEDP of both 30 and 50 mmHg, the DNA-binding activity of HSF1was 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 afterloadedhearts, with the perfusion of norepinephrine, the activation of HSF was not induced. Conclusion: Our findings demonstrate that increased preloadas mechanical stress directly induces the activation of HSF1in the LV-overloaded heart.