Inhibition of Myocardial TNF‐α Production by Heat Shock: A Potential Mechanism of Stress‐Induced Cardioprotection against Postischemic Dysfunctiona

Abstract

Overproduction of tumor necrosis factor‐α (TNF‐α) contributes to cardiac dysfunction associated with systemic or myocardial stress, such as endotoxemia and myocardial ischemia/reperfusion (I/R). Heat shock has been demonstrated to enhance cardiac functional resistance to I/R. However, the protective mechanisms remain unclear. The purpose of this study was to determine: (1) whether cardiac macrophages express heat shock protein 72 (HSP72) after heat shock, (2) whether induced cardiac HSP72 suppresses myocardial TNF‐a production during I/R, and (3) whether preservation of postischemic myocardial function by heat shock is correlated with attenuated TNF‐a production during I/R. Rats were subjected to heat shock (42°C for 15 min) and 24 h recovery. Immunoblotting confirmed the expression of cardiac HSP72. Immunofluorescent staining detected HSP72 in cardiac interstitial cells including resident macrophages rather than myocytes. Global I/R caused a significant increase in myocardial TNF‐α. The increase in myocardial TNF‐α was blunted by prior heat shock and the reduced myocardial TNF‐α level was correlated with improved cardiac functional recovery. This study demonstrates for the first time that heat shock induces HSP72 in cardiac resident macrophages and inhibits myocardial TNF‐a production during I/R. These observations suggest that inhibition of myocardial TNF‐a production may be a mechanism by which HSP72 protects the heart against postischemic dysfunction.