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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Heilmann
Claudia
C
Department of Cardiovascular Surgery, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
von Samson
Patrick
P
Schlegel
Kerstin
K
Attmann
Tim
T
von Specht
Bernd Ulrich
BU
Beyersdorf
Friedhelm
F
Lutter
Georg
G
D000818:Animals; D002908:Chronic Disease; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2