Improvement of contractility accompanies angiogenesis rather than arteriogenesis in chronic myocardial ischemia.
BACKGROUND
Growth factor therapy provides a therapeutic alternative for "no option" patients with coronary disease. Fibroblast Growth Factor-2 (FGF-2) predominantly stimulates angiogenesis, the growth of new capillaries, whereas Monocyte Chemoattractant Protein-1 (MCP-1) is considered an arteriogenic agent. We hypothesised a synergetic effect of FGF-2 and MCP-1 in ischemic myocardium.


METHODS
A severe coronary stenosis was created in pigs. After one week, chronic ischemia was confirmed by angiography, echocardiography, reduced ejection fraction, and increase of marker enzymes. FGF-2, MCP-1, both, or vector only were then injected intramyocardially as plasmid DNA in the impaired area. Regional contractility and number of capillaries and arterial vessels were evaluated after three months.


RESULTS
FGF-2, FGF-2+MCP-1, and vector, but not MCP-1 alone improved regional contractility at rest, whereas only FGF-2 alone ameliorated function under stress conditions. Angiogenesis in the ischemic area was stimulated by FGF-2 compared to MCP-1. In contrast, MCP-1 induced arteriogenesis relative to FGF-2.


CONCLUSIONS
Differences for vessel growth and regional function were apparent between FGF-2 and MCP-1. This contrast could allow the speculation that development of a flow reserve in chronically ischemic myocardium is linked to angiogenesis rather than to arteriogenesis. No additional benefits were seen following combined therapy.
Heilmann
Claudia
C
Department of Cardiovascular Surgery, University Hospital Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany. heilmann@ch11.ukl.uni-freiburg.de
Kostic
Caterina
C
Giannone
Bodo
B
Grawitz
Andrea Busse
AB
Armbruster
Werner
W
Lutter
Georg
G
Beyersdorf
Friedhelm
F
Göbel
Heike
H
D000818:Animals; D002196:Capillaries / Q000254:growth & development; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D002908:Chronic Disease; D023921:Coronary Stenosis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D003331:Coronary Vessels / Q000254:growth & development; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic; D013552:Swine
D018932:Chemokine CCL2; D036341:Intercellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2