Adenovirus-mediated gene transfer of a heat shock protein 70 (hsp 70i) protects against simulated ischemia.
We have recently shown that the overexpression of a heat shock protein 70 (hsp 70) in a rat myogenic cell line confers protection against simulated ischemia. We also developed and demonstrated that overexpression of this protein, in the hearts of transgenic mice, protects against ischemia/reperfusion injury. We 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 adenoviral-hsp70i construct are rendered tolerant to simulated ischemia as compared to cells infected with a control recombinant adenoviral construct. In conclusion, our results demonstrate the feasibility of using adenoviral vectors to overexpress the hsp70 in myogenic cells, specially in cardiomyocytes, and the efficiency of this approach for providing protection against myocardial ischemia.
Mestril
R
R
Department of Medicine, University of California, San Diego, La Jolla 92093-0618, USA.
Giordano
F J
FJ
Conde
A G
AG
Dillmann
W H
WH
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007511:Ischemia; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics
D018840:HSP70 Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase