Expression of inducible stress protein 70 in rat heart myogenic cells confers protection against simulated ischemia-induced injury

Myocardial ischemia markedly increases the expression of sev-eral members of the stress/heat shock protein (HSP) family, especially the inducible HSP70 isoforms. Increased expression ofHSP70 has been shown to exert a protective effect against a lethal heat shock. We have examined the possibility of using this resistance to a lethal heat shock as a protective effect against an ischemic-like stress in vitro using a rat embryonic heart-derived cell line H9c2(2-1). Myogenic cells in which the heat shock proteins have been induced by a previous heat shock are found to become resistant to a subsequent simulated isch-emic stress. In addition, to address the question of how much does the presence of the HSP70 contribute to this protective effect, we have generated stably transfected cell lines overex-pressing the human-inducible HSP70. Embryonal rat heart-derived H9c2(2-1) cells were used for this purpose. This stably transfected cell line was found to be significantly more resistant to an ischemic-like stress than control myogenic cells only ex-pressing the selectable marker (neomycin) or the parental cell line H9c2(2-1). This finding implicates the inducible HSP70 protein as playing a major role in protecting cardiac cells against ischemic injury. (J. Clin. Invest. 1994. 93:759-767.) Key words: heat shock proteins * thermotolerance * myocardial ischemia * hypoxi