Intramyocardial injection of low-dose basic fibroblast growth factor or vascular endothelial growth factor induces angiogenesis in the infarcted rabbit myocardium.
BACKGROUND
Myocardial angiogenesis after the systemic administration of basic fibroblast growth factor or vascular endothelial growth factor at high therapeutic doses has been implicated in the occurrence of side effects that may undermine their safety. The aim of this study was to investigate the angiogenic effects of the intramyocardial administration of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, at low doses, in the infarcted rabbit myocardium.


RESULTS
Twenty-five New Zealand White rabbits were divided into five groups (n=5) and subjected to coronary artery ligation after lateral thoracotomy, inducing acute myocardial infarction. Five minutes later, the following substances were injected intramyocardially into the infarcted area: (a) normal saline (controls); (b) 6.25 or 12.5 mug of recombinant human basic fibroblast growth factor protein (basic fibroblast growth factor-1 group or basic fibroblast growth factor-2 group); or (c) 5 or 10 microg of recombinant human vascular endothelial growth factor 165 protein (vascular endothelial growth factor-1 group or vascular endothelial growth factor-2 group). On the 21st postoperative day, the animals were euthanized, and their hearts were subjected to histopathological examination and immunohistochemical assessment of vascular density in the infarcted area. The alkaline phosphatase anti-alkaline phosphatase procedure and the primary monoclonal antibody JC70 were used. Histopathological examination confirmed the induction of myocardial infarction. Vascular density was significantly increased (P<.004) in all treatment groups (in mean+/-S.E. vessels/x 200 optical field: basic fibroblast growth factor-1: 85.8+/-10.9; basic fibroblast growth factor-2: 76.6+/-3.7; vascular endothelial growth factor-1: 73.4+/-3.2; vascular endothelial growth factor-2: 89.5+/-5.2) compared to that in controls (58.9+/-4.9 vessels/x 200 optical field). Vascular density in the vascular endothelial growth factor-2 group was significantly higher than that in the vascular endothelial growth factor-1 group (P<.001).


CONCLUSIONS
Low doses of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, when administered intramyocardially, stimulate angiogenesis in the infarcted myocardium.
Bougioukas
Ioannis
I
Department of Cardiothoracic Surgery, School of Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Dragana, 68 100 Alexandroupolis, Greece. gbougiou@med.duth.gr
Didilis
Vassilios
V
Ypsilantis
Petros
P
Giatromanolaki
Alexandra
A
Sivridis
Efthimios
E
Lialiaris
Theodoros
T
Mikroulis
Dimitrios
D
Simopoulos
Constantinos
C
Bougioukas
Georgios
G
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D007124:Immunoenzyme Techniques; D015552:Injections, Intralesional; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1