Adenoviral PR39 improves blood flow and myocardial function in a pig model of chronic myocardial ischemia by enhancing collateral formation

• DOI: 10.1152/ajpregu.00460.2005
• Publication Date: 2005-10-28T00:40:30Z
• Authors: Mark J. Post; Kaori Sato; Masahiro Murakami; Jialin Bao; Daniela Tirziu; Justin D. Pearlman; Michael Simons
• Keywords: Collateral circulation

Angiogenic therapy with individual growth factors or "master switch" genes is being evaluated for treatment of advanced coronary artery disease. In this study, we investigated the efficacy and mechanism PR39, a gene capable activating VEGF fibroblast factor (FGF)-2-dependent pathways. PR39 enhances hypoxia-inducible factor-1alpha (HIF-1alpha)-dependent expression by selectively inhibiting proteasome degradation transcription factor. addition, also stimulates FGF receptors (FGFR)-1 syndecan-4. pig model chronic myocardial ischemia, used angiography, MRI, microsphere regional blood flow to evaluate intramyocardial adenoviral protein arginine-rich peptide (Ad-PR39) injections. Ad-PR39 improved collateral scores, perfusion, function in dose-dependent manner. Local VEGF, VEGFR-1, VEGFR-2, syndecan, FGFR-1 levels were 16-75% upregulated after injections as assessed real-time PCR, suggesting upregulation an angiogenic that improves perfusion ischemic myocardium, at least part, through formation. The dual mechanism, i.e., stimulation HIF-1alpha receptor expression, likely accounts functional benefits PR39.