title: Hypoxia-inducible factor 1-alpha reduces infarction and attenuates progression of cardiac dysfunction after myocardial infarction in the mouse.
abstract: OBJECTIVE
  The aim of this research was to test whether constitutive expression of hypoxia-inducible factor 1-alpha (HIF-1alpha) influences infarction size and cardiac performance after myocardial infarction.
  
  
  BACKGROUND
  A major question in clinical medicine is whether infarction size and border zone remodeling of the heart can be influenced by the overexpression of specific genes in the peri-infarction region.
  
  
  METHODS
  We investigated the role of constitutive HIF-1alpha expression in acute myocardial infarction using a transgenic model. Transgenic mice containing the HIF-1alpha gene under the control of the alpha-myosin heavy chain promoter were constructed. Myocardial infarction was produced by coronary ligation in HIF-1alpha transgenic mice and control animals. Extent of infarction was then quantitated by two-dimensional and M-mode echocardiography as well as by molecular and pathologic analysis of heart samples in infarct, peri-infarct, and remote heart regions at serial time points.
  
  
  RESULTS
  Constitutive overexpression of HIF-1alpha in the murine heart resulted in attenuated infarct size and improved cardiac function 4 weeks after myocardial infarction. Significantly, we found an increase in both capillary density as well as vascular endothelial growth factor and inducible nitric oxide synthase expression in peri-infarct and infarct regions in the hearts of constitutive HIF-1alpha-expressing animals compared to control animals.
  
  
  CONCLUSIONS
  These observations suggest the involvement of HIF-1alpha in myocardial remodeling and peri-infarct vascularization. Our results show that supranormal amounts of this peptide protect against extension of infarction and improve border zone survival in myocardial infarction.
authors.affiliation: Division of Cardiothoracic Surgery, University of California, San Diego, San Diego, California 92103-8892, USA.
authors.forename: Masakuni
authors.initials: M
authors.lastname: Kido
authors.forename: Lingling
authors.initials: L
authors.lastname: Du
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Sullivan
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Reena
authors.initials: R
authors.lastname: Deutsch
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Jamieson
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Thistlethwaite
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D018450:Disease Progression; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D052247:Nitric Oxide Synthase Type II