The efficacy of a ‘master switch gene’ HIF-1α in a porcine model of chronic myocardial ischaemia
| Autor: | Jie Zhu, Amanda Heinl-Green, Felix M. Munkonge, Peter W. Radke, Oliver M. Frass, Eric W.F.W. Alton, Duncan M. Geddes, Karen Vincent |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Pathology Swine Genetic enhancement medicine.medical_treatment Genetic Vectors Myocardial Ischemia Neovascularization Physiologic Gene delivery Revascularization Models Biological Neovascularization Random Allocation Coronary Circulation Internal medicine medicine Animals Therapeutic angiogenesis business.industry Gene Transfer Techniques Genetic Therapy Hypoxia-Inducible Factor 1 alpha Subunit Immunohistochemistry Hypoxia-inducible factors Echocardiography Chronic Disease Circulatory system Cardiology medicine.symptom Cardiology and Cardiovascular Medicine business Perfusion Genes Switch Transcription Factors |
| Zdroj: | European Heart Journal. 26:1327-1332 |
| ISSN: | 1522-9645 0195-668X |
| DOI: | 10.1093/eurheartj/ehi223 |
| Popis: | 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).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.Ad2/HIF-1alpha increased myocardial perfusion and improved LV function. Plasmid HIF-1alpha was not associated with improvements in any bioactivity endpoints. |
| Databáze: | OpenAIRE |
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