Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Heinl-Green, A. et al.

Heinl-Green, Radke, Munkonge, Frass, Zhu, Vincent, Geddes, Alton,

The efficacy of a 'master switch gene' HIF-1alpha in a porcine model of chronic myocardial ischaemia.

AIMS: Therapeutic angiogenesis is a potential new treatment for patients unsuitable for conventional revascularization strategies. We investigated angiogenesis via a 'master switch gene' hypoxia inducible factor (HIF-1alpha). METHODS AND RESULTS: Ameroid occluders were placed around the left circumflex coronary artery of 74 pigs. Three weeks later, pigs were randomized to receive (i) adenovirus encoding HIF-1alpha (Ad2/HIF-1alpha VP-16 10(10) particles); (ii) plasmid DNA encoding HIF-1alpha (pHIF-1alpha NFkappaB 500 microg); (iii) pHIF-1alpha NFkappaB 2500 microg; and (iv) adenoviral control (Ad2/CMV-empty vector 10(10) particles). Twenty injections (50 microL each) were administered epicardially via re-thoracotomy. Three weeks after gene delivery significant (ANOVA P=0.02) changes in myocardial perfusion during stress were seen in the area adjacent to injections. Post hoc testing (Bonferroni) demonstrated that the AdHIF-1alpha group was significantly (P=0.02) different from the Ad2/control. There were also significant (ANOVA P=0.02) differences in resting left ventricular (LV) function. Post hoc (Bonferroni) showed that the AdHIF-1alpha group was significantly different from the Ad2/control (P=0.03). No significant changes in any parameter were seen with plasmid HIF-1alpha. There were no differences in collateralization or capillary growth. CONCLUSION: Ad2/HIF-1alpha increased myocardial perfusion and improved LV function. Plasmid HIF-1alpha was not associated with improvements in any bioactivity endpoints.[1]

References

The efficacy of a 'master switch gene' HIF-1alpha in a porcine model of chronic myocardial ischaemia. Heinl-Green, A., Radke, P.W., Munkonge, F.M., Frass, O., Zhu, J., Vincent, K., Geddes, D.M., Alton, E.W. Eur. Heart J. (2005) [Pubmed]

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