The aim of this research was to test whether constitutive expression of hypoxia-inducible factor 1-alpha (HIF-1α) influences infarction size and cardiac performance after myocardial infarction.

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.

We investigated the role of constitutive HIF-1α expression in acute myocardial infarction using a transgenic model. Transgenic mice containing the HIF-1α gene under the control of the α-myosin heavy chain promoter were constructed. Myocardial infarction was produced by coronary ligation in HIF-1α 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.

Constitutive overexpression of HIF-1α 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-1α–expressing animals compared to control animals.

These observations suggest the involvement of HIF-1α 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.