Presence of heat shock protein 72 in cardiomyocytes after heat stress.

Cardiomyocytes After Heat Stress To the Editor: It is well-known that prior in vivo heat stress induces the synthesis of heat shock protein (HSP) 72 in the rat heart, but the precise content in the various cell-types has not yet been measured. It is therefore of great importance to conduct experiments as performed in the paper by Leger et al.1 However, the overall conclusion that heat pretreatment does not lead to HSP72 synthesis in cardiomyocytes is unjustified. In addition, the statement that blood vessels play a primary role in the heat shock–induced cardioprotection is preliminary. The double-labeling experiments of Leger et al,1 staining HSP72, as well as HSP27, clearly indicates the presence of both proteins in the same area, which the authors define as cardiomyocytes in the case of HSP27. Indeed, other studies indicate that cardiomyocytes do overexpress HSP72 after stress: cardiomyocytes of intact hearts are capable of overexpressing HSP72 after heat treatment.2 Although the increase of HSP72 normalized for protein content was lower in cardiomyocytes than in endothelial cells, the absolute HSP72 amount was 3 times higher in the cardiomyocyte than in the endothelial cell pool. Furthermore, isolated cardiomyocytes increase their synthesis of HSP72 either after heat shock or hypoxia.3 Lastly, in cardiomyocytes, an enhanced HSP72 presence has been documented immunohistochemically after ischemia/reperfusion, after application of a nitric oxide donor, and after aortic stenosis.4,5 Because of the similar response against various stresses, it is conceivable that heat pretreatment should provoke enhanced HSP72 synthesis in cardiomyocytes. The authors should have verified the relative HSP72 amounts in cardiomyocyte and endothelial cell fractions and the endothelial specific HSP72 expression. The authors’ statement that the beneficial effects of heat pretreatment on ischemia/reperfusion tolerance are almost exclusively due to the HSP72-induction in endothelial cells is premature. To prove this hypothesis, transgenic mice overexpressing HSP72 exclusively in endothelial cells should be generated and tested for ischemia/ reperfusion tolerance. Furthermore, we do not know to what extent the increased functional recovery of the heat-pretreated hearts after ischemia/reperfusion is dependent on its absolute HSP72 content. Experiments specifically blocking the increase in HSP72-synthesis in cardiomyocytes after heat treatment would help to understand the contribution of HSP72 synthesis in these cells leading to enhanced ischemia and reperfusion tolerance.3 In our opinion, the conclusions of Leger and coworkers should be substantiated by experiments, providing exclusive evidence that heat shock–induced enhanced HSP72 expression in the endothelial cell compartment, and not in the cardiomyocyte, is responsible for the improved ischemia/reperfusion tolerance of the heart.