Hypoxia-inducible factor 1-alpha reduces infarction and attenuates progression of cardiac dysfunction after myocardial infarction in the mouse

J Am Coll Cardiol. 2005 Dec 6;46(11):2116-24. doi: 10.1016/j.jacc.2005.08.045. Epub 2005 Nov 9.


Objectives: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Disease Progression
  • Hypoxia-Inducible Factor 1 / metabolism
  • Hypoxia-Inducible Factor 1 / physiology*
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Transgenic
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / pathology
  • Myocardium / metabolism*
  • Neovascularization, Physiologic / physiology
  • Nitric Oxide Synthase Type II / metabolism
  • Transcription, Genetic / physiology
  • Vascular Endothelial Growth Factor A / metabolism
  • Ventricular Function, Left
  • Ventricular Remodeling / physiology


  • Hypoxia-Inducible Factor 1
  • Vascular Endothelial Growth Factor A
  • Nitric Oxide Synthase Type II