Comparison of protein with DNA therapy for chronic myocardial ischemia using fibroblast growth factor-2.

Abstract

Treatment of coronary disease by growth factors has become an increasingly used strategy for otherwise untreatable patients and is subject to a number of clinical studies. The aim is to stimulate the development of a sufficient collateral circulation and hereby to rescue cardiac function. The objective of our study was to compare the effectiveness of fibroblast growth factor-2 (FGF-2) as protein and as naked plasmid DNA in a porcine model of chronic myocardial ischemia. A severe stenosis of the left anterior descending artery (LAD) artery was created in healthy pigs. After 1 week, perfusion and regional and global contractility was assessed at baseline at rest and under stress. Afterwards, recombinant FGF-2 (n=6) or naked plasmid DNA encoding FGF-2 (n=7) was intramyocardially injected into the LAD territory. Control animals were left untreated (n=5). After 3 months, the animals were re-examined and underwent immunohistologic analysis. One animal received an Enhanced Green Fluorescent Protein plasmid. Plasmid-dependent protein synthesis was present in cardiomyocytes. FGF-2 protein as well as plasmid injections resulted in an increased number of capillaries and of arterioles compared with untreated ischemia. The improvement of the regional myocardial blood flow by FGF-2 plasmid therapy at rest might however indicate the effectiveness of the DNA application for the induction of a collateral circulation. A benefit from FGF-2 plasmid therapy was revealed with regard to regional contractility. Systemic hemodynamics were partially improved following plasFGF-2 treatment. In this porcine model of chronic myocardial ischemia, intramyocardial injection of FGF-2 plasmid was more effective than of FGF-2 protein in improving regional perfusion and contractility compared to untreated ischemia.