HEAT-SHOCK PROTEINS IN MYOCARDIAL STRESS

In this overview four questions were discussed related to heat shock p roteins and myocardial ischemia. Heat shock proteins are chaperones wh ich associate with malfolded proteins and prevent their aggregation in to larger damaging complexes. In myocardial ischemia, the inducible he at shock protein 70 (hsp70), the mitochondrial heat shock protein 60 a nd the small 27 heat shock protein increases after 30 minutes of ische mia of the rat heart and subsequent reperfusion. In addition, we descr ibe direct evidence for the protective effect of heat shock proteins a gainst simulated ischemia in H9c2 cells. H9c2 cells are an embryonal r at heart derived permanent cell line which maintains some features of cardiac myocytes. Making stable lines overexpressing the inducible hsp 70 we could show that simulated ischemia leads to less injury in H9c2 cells overexpressing the hsp70 transgene. In addition, transgenic mice were constructed in which the rat inducible hsp70 is induced in cardi ac myocytes. Submitting such hearts in a Langendorf isolated heart per fusion set-up to 20 minutes of global ischemia and following the contr actile recovery of the heart, we found that in transgenic mouse hearts contractile recovery was significantly enhanced. Furthermore in heart s from transgenic mice overexpressing the inducible hsp70, less CK rel ease occurs and infarct size was decreased. In summary, increased expr ession of the inducible hsp70 exerts a protective effect against the i njury induced by myocardial ischemia.