title: In vivo gene delivery of HSP70i by adenovirus and adeno-associated virus preserves contractile function in mouse heart following ischemia-reperfusion.
abstract: 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 that constitutively overexpress 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 left ventricular 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-mo 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 (preischemic) 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 min 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.
authors.affiliation: Dept. of Medicine, University of California, San Diego, La Jolla, CA 92093-0618, USA.
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Belke
authors.forename: Bernd
authors.initials: B
authors.lastname: Gloss
authors.forename: John M
authors.initials: JM
authors.lastname: Hollander
authors.forename: Eric A
authors.initials: EA
authors.lastname: Swanson
authors.forename: Hervé
authors.initials: H
authors.lastname: Duplain
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Dillmann
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006352:Heart Ventricles / Q000821:virology; D007763:Lac Operon / Q000235:genetics / Q000502:physiology; D051379:Mice; D009200:Myocardial Contraction / Q000235:genetics / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016276:Ventricular Function
chemical_list: D018840:HSP70 Heat-Shock Proteins