The efficacy of a 'master switch gene' HIF-1α 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-1 alpha). 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-1 alpha (Ad2/HIF-1 alpha VP-16 1010 particles); (ii) plasmid DNA encoding HIF-1a (pHIF-1 alpha NF kappa B 500 [mu g); (iii) pH[F-l(x NF kappa B 2500 mu g; and (iv) adenoviral control (Ad2/CMV-empty vector 10(10) particles). Twenty injections (50 mu L 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 AdHlF-1 alpha 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 AdHlF-1 alpha group was significantly different from the Ad2/control (P = 0.03). No significant changes in any parameter were seen with plasmid HIF-1 alpha. There were no differences in collateralization or capillary growth. Conclusion Ad2/HlF-1 alpha increased myocardial. perfusion and improved LV function. Plasmid HIF-1 alpha was not associated with improvements in any bioactivity endpoints.