Heat shock proteins and the ischemic heart. An endogenous protective mechanism.

P rotection of the ischemic heart has been the subject of experimental and clinical research for more than a decade. Myocardial infarct size is a function of cell necrosis occurring during ischemial and reperfusion,2 and numerous investigators have attempted to limit ischemic-and reperfusion-induced injury by pharmacological means. On balance, if the number of articles indicating successful intervention may be considered the arbiter of consensus, then it is unequivocal that ischemic-and reperfusion-induced injury can be attenuated pharmacologically and by induction of a preconditioning ischemic or thermal stress in experimental animal models. However, no drug has yet been approved for use as an "anti-ischemic" agent or as a cardioprotective adjunct to thrombolytic/angioplasty treatment (excepting antithrombotic drugs). The approach taken by Currie and colleagues, as reported in this issue of Circulation3 (and elsewhere4-7), to limit ischemic heart damage is unique in that protection of See p 963 the ischemic heart is afforded by an incompletely understood endogenous mechanism activated by whole-body heat shock. Raising the body temperature of anesthetized animals to 420C for a period of 15 minutes (heat shock) protects the heart against an ischemic insult.4 Currie and coworkers3 demonstrate that whole-body heat shock is protective against ischemia/reperfu-sion injury in vivo, confirming previous studies of car-dioprotection against in vitro ischemic injury.4-6 Heat shock-mediated cardioprotection in vivo is transient, and the observed protective effect is no longer present 40 hours after application of the initial heat stress. The hypothesis supported by current3 and previous4'8.9 studies is that myocardial protection is related to the heat shock-mediated increase in cardiac heat shock protein synthesis. The term "heat shock protein" (HSP) refers to a group of proteins of which there are several families, differentiated by molecular weight (i.e., HSP 60, HSP 70, and HSP 90 families). Within families of HSP are subsets; constitutively expressed proteins are referred to as heat shock cognates (HSCs), whereas proteins ex-The opinions expressed in this editorial comment are not necessarily those of the editors or of the American Heart Association. pressed largely under conditions of stress are referred to as the HSPs.10 Members of this latter group also may be expressed at a lower level under nonstressed conditions. Cells exposed to elevated temperature, ethanol, heavy metals, or other noxious stimuli show increased expression of HSPs. HSCs and constitutively expressed HSPs function under nonstressed conditions in cells to prevent misfolding or aggregation of nascent polypeptides, allowing polypeptides to traverse biomembranes and promoting …