Hypoxia-Inducible Factor 1-Alpha Reduces Infarction and Attenuates Progression of Cardiac Dysfunction After Myocardial Infarction in the Mouse Original Research Article

Objectives 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. 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-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. Results 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. Conclusions 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.