Role Of HSP70 In Cardiovascular Mechanism Of Cross-adaptation And Its Signal Transduction Regulation

Objective: To investigate the pattern of cardiovascular activity in rats during formation of restraint-heat cross-adaptation and explore the role of HSP70 in cardiovascular mechanism of cross-adaptation and its signal transduction pathways, so as to provide new idea for prevention and treatment of stress-induced cardiovascular diseases. Methods: To identify whether the restraint-heat cross-adapted rat model was established, rectal temperature and content of catecholamine in plasma were examined. The heart rate, blood pressure and ECG were measured by multichannel physiograph and blood pressure-thermometer to investigate the pattern of cardiovascular activity in cross-adaptation. Expression of HSP70 in myocardial cell was measured by western blot method, and the effects of different expression levels of HSP70 on LDH activity in the medium, cell death rates, cardiovascular function of cross adapted animal by treating with recombinant adenovirus (Ad5.asHsp70) were determined to study the molecular basis in cardiovascular mechanism of cross-adaptation. The influence of activation of ERK signal transduction pathway on the binding activity of HSF1 to HSE derived from the promoter of HSP70 in cardiomyocyte was analysed by Electophoretic Mobility Shift Assay (EMSA) to study further the signal transduction regulation mechanism of HSP70expression in cardiomyocyte of cross-adaptation. Results: ?The restraint-heat cross-adapted animal model was established by 6h restraint stress per day for 2 weeks. (2) The cardiovascular adaptive regulation which could significantly decrease the disorder of cardiac function and injury to cardiomyocyte played an important role in the formation of cross-adaptation. (3)HSP70 expression was significantly increased in cross-adapted cardiomyocytes in vivo and in vitro, and the phenomenon of cross-adaptation of restrain-heat stress disappeared after HSP70 expression wasinhibited by recombinant adenovirus, indicating that HSP70 expression may be one of the molecular mechanism of the formation of cross-adaptation. (4) The activation of ERK signal transduction pathway may not be the main regulatory factor of HSF1-HSE mediated HSP70 expression signal transduction pathway. ConcIusion:Restraint adaptation can induce the formation of cross-adaptation to heat stress. HSP70 expression which plays an important role in cardiovascular mechanism in cross-adaptation is the important molecular basis of adaptive regulation mechanism of cardiovascular system. ERK signal transduction pathway may not play an important role in HSP70 expression regulation in cardiomyocytes of cross-adaptation.