ADENOVIRUS-MEDIATED GENE-TRANSFER OF A HEAT-SHOCK-PROTEIN-70 (HSP70I)PROTECTS AGAINST SIMULATED ISCHEMIA

We have recently shown that the overexpression of a heat shock protein 70 (hsp70) in a rat myogenic cell line confers protection against sim ulated ischemia. Mie also developed and demonstrated that overexpressi on of this protein, in the hearts of transgenic mice, protects against ischemia/reperfusion injury. Mie have now inserted the hsp70 gene in an adenoviral vector and show that we are able to transfer and achieve overexpression of this protein in neonatal cardiomyocytes and in the rat myogenic cell line H9c2. We find that cells infected with the aden oviral-hsp70i construct are rendered tolerant to simulated ischemia as compared to cells infected with a control recombinant adenoviral cons truct. In conclusion, our results demonstrate the feasibility of using adenoviral vectors to overexpress the hsp70 in myogenic cells, specia lly in cardiomyocytes, and the efficiency of this approach for providi ng protection against myocardial ischemia. (C) 1996 Academic Press Lim ited.