title: A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo.
abstract: OBJECTIVE
  The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed.
  
  
  BACKGROUND
  When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector'' system that amplifies cardioprotective gene expression.
  
  
  METHODS
  Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed.
  
  
  RESULTS
  Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling.
  
  
  CONCLUSIONS
  The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, University of South Florida, St. Petersburg, FL, USA.
authors.forename: Yao Liang
authors.initials: YL
authors.lastname: Tang
authors.forename: Keping
authors.initials: K
authors.lastname: Qian
authors.forename: Y Clare
authors.initials: YC
authors.lastname: Zhang
authors.forename: Leping
authors.initials: L
authors.lastname: Shen
authors.forename: M Ian
authors.initials: MI
authors.lastname: Phillips
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D005822:Genetic Vectors; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D000860:Hypoxia; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control* / Q000628:therapy; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010957:Plasmids; D020257:Ventricular Remodeling
chemical_list: D051547:Heme Oxygenase-1