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Am J Physiol Heart Circ Physiol (August 18, 2006). doi:10.1152/ajpheart.00323.2006
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Submitted on March 28, 2006
Accepted on August 1, 2006

In Vivo Gene Delivery of HSP70i by Adenovirus and Adeno-Associated Virus Preserves Contractile Function in Mouse Heart Following Ischemia-Reperfusion

Darrell D Belke1*, Bernd Gloss1, John M Hollander2, Eric A Swanson1, Herve Duplain1, and Wolfgang H. Dillmann3

1 Medicine, UCSD, San Diego, California, United States
2 Exercise Physiology, West Virginia University, Morgantown, West Virginia, United States
3 Department of Medicine, University of California, La Jolla, California, United States; Medicine, UCSD, San Diego, California, United States

* To whom correspondence should be addressed. E-mail: dbelke{at}ucsd.edu.

Inducible heat shock protein 70 (HSP70i) has been shown to exert a protective effect in hearts subjected to ischemia-reperfusion. Although studied in heat shocked animals and in transgenic mice which constitutively over-express the protein, the therapeutic application of the protein in the form of a viral vector-mediated HSP70i expression has not been widely examined. Accordingly, we have examined the effects of HSP70i delivered in vivo to the LV free wall of the heart via viral gene therapy in mice. The affect of virally mediated HSP70i expression in preserving cardiac function following ischemia-reperfusion was examined after short-term expression (5 day adenovirus-mediated) and long-term expression (8 months adeno-associated virus-mediated) in mice by subjecting ex vivo Langendorff perfused hearts to a regime of ischemia-reperfusion. Both vectors were capable of increasing HSP70i expression in the heart, and neither vector had any effect on cardiac function during aerobic (pre-ischemic) perfusion when compared with corresponding controls. In contrast, both adenovirus-mediated and adeno-associated virus-mediated expression of HSP70i improved the contractile recovery of the heart after 120 minutes of reperfusion following ischemia. This study demonstrates the feasibility of using both short and long-term expression of virally-mediated HSP70i as a therapeutic intervention against cardiac ischemia-reperfusion injury.




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