title: In vivo gene delivery of XIAP protects against myocardial apoptosis and infarction following ischemia/reperfusion in conscious rabbits.
abstract: OBJECTIVE
  We tested the hypothesis that an in vivo gene delivery of the pro-survival protein XIAP (X-chromosome linked inhibitor of apoptosis protein) protects against myocardial apoptosis and infarction following ischemia/reperfusion.
  
  
  METHODS
  Nineteen rabbits were chronically instrumented with a hydraulic occluder placed around the circumflex coronary artery. Adenovirus harboring XIAP (Ad.XIAP; 1×10(10)pfu/ml) or β-galactosidase (5×10(9)pfu/ml), as a control, was constructed and transfected into the heart using a catheter placed into the left ventricle accompanied by cross-clamping. 1-2weeks after gene delivery, myocardial ischemia was induced by a 30-min occlusion followed by reperfusion for four days. Protein expression was determined by Western blot and apoptosis (% of myocytes) was quantified by TUNEL staining.
  
  
  RESULTS
  Myocardial infarct size, expressed as a fraction of the area at risk, was reduced in Ad.XIAP (n=5) compared to control (n=7) rabbits (21±3% vs. 30±2%, p<0.05). Apoptosis was reduced in Ad.XIAP rabbits compared to control rabbits (2.96±0.68% vs. 8.98±1.84%, p<0.01). This was associated with an approximate 60% decrease in the cleaved caspase-3 level in Ad.XIAP rabbits compared to control rabbits.
  
  
  CONCLUSIONS
  The current findings demonstrate that overexpression of XIAP via in vivo delivery in an adenovirus can reduce both myocardial apoptosis and infarction following ischemia/reperfusion, at least in part, due to the ability of XIAP to inhibit caspase-3. These findings confirm previous work suggesting a link between myocardial apoptosis and infarction i.e., anti-apoptotic therapy was effective in reducing myocardial infarct size.
authors.affiliation: Section of Cardiology, Advocate Illinois Masonic Medical Center, University of Illinois, Chicago, IL 60657, United States. kimso@uic.edu
authors.forename: Song-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Alex
authors.initials: A
authors.lastname: Kuklov
authors.forename: George J
authors.initials: GJ
authors.lastname: Crystal
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D020287:In Situ Nick-End Labeling; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D014162:Transfection; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*
chemical_list: D051636:X-Linked Inhibitor of Apoptosis Protein; D053148:Caspase 3