Heat shock proteins in myocardial stress.
In this overview four questions were discussed related to heat shock proteins and myocardial ischemia. Heat shock proteins are chaperones which associate with malfolded proteins and prevent their aggregation into large damaging complexes. In myocardial ischemia, the inducible heat shock protein 70 (hsp70), the mitochondrial heat shock protein 60 and the small 27 heat shock protein increases after 30 minutes of ischemia of the rat heart and subsequent reperfusion. In addition, we describe direct evidence for the protective effect of heat shock proteins against simulated ischemia in H9c2 cells. H9c2 cells are an embryonal rat heart derived permanent cell line which maintains some features of cardiac myocytes. Making stable lines overexpressing the inducible hsp70 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 cardiac myocytes. Submitting such hearts in a Langendorf isolated heart perfusion set-up to 20 minutes of global ischemia and following the contractile recovery of the heart, we found that in transgenic mouse hearts contractile recovery was significantly enhanced. Furthermore in hearts from transgenic mice overexpressing the inducible hsp70, less CK release occurs and infarct size was decreased. In summary, increased expression of the inducible hsp70 exerts a protective effect against the injury induced by myocardial ischemia.
Dillmann
W H
WH
Dept. of Medicine, University of California, San Diego Medical Center 92103-8412, USA.
Mestril
R
R
D000818:Animals; D002460:Cell Line; D015870:Gene Expression / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000235:genetics; D017202:Myocardial Ischemia / Q000235:genetics*; D015428:Myocardial Reperfusion Injury / Q000235:genetics; D009206:Myocardium / Q000473:pathology; D051381:Rats
D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins