Effect of basic fibroblast growth factor on angiogenesis in the infarcted porcine heart.
Administration of growth factors is emerging as a new therapeutic approach for the enhancement of collateral vessel formation in the ischemic heart. We have investigated the effects of intramyocardial delivery of FGF-2 in the presence and absence of heparin on angiogenesis in a porcine model of myocardial infarction. Yorkshire pigs were subjected to myocardial infarction by the placement of an embolization coil in the left anterior descending artery (n = 5). Four to five weeks after creation of an infarct, FGF-2 (10 micrograms) alone or in complex with heparin, heparan sulfate, or heparin agarose beads was injected either into the normal myocardium or along the infarct border area. Histologic evaluation of each injection site was performed 4 to 5 weeks post-injection. The effect of FGF-2 on angiogenesis was evaluated by determining the number of capillaries (diameter < 20 microns (and arterioles (> 20 microns with tunica media) in each area observed. The number of capillaries were not affected by the treatment of FGF-2 both in normal myocardium and infarct border area. However, in the normal myocardium, the number of arterioles were increased with the treatment of FGF-2 alone (85 +/- 59%, P < 0.04), FGF-2 plus heparin (281 +/- 193%, P < 0.004) and FGF-2-coated heparin beads (241 +/- 141%, P < 0.01), as compared to control. Delivery of FGF-2 into the infarct border area, also increased the number of arterioles when FGF-2 was given with heparin (736 +/- 154%, P < 0.001) or heparin beads (700 +/- 109%, P < 0.001), as compared to control. FGF-2 administered with heparin was the most effective method of enhancing angiogenesis as compared to FGF-2 alone, FGF-2 plus heparan sulfate, or FGF-2 coated heparin agarose beads.
Watanabe
E
E
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70112, USA.
Smith
D M
DM
Sun
J
J
Smart
F W
FW
Delcarpio
J B
JB
Roberts
T B
TB
Van Meter
C H
CH
Claycomb
W C
WC
D000345:Affinity Labels / Q000494:pharmacology; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003097:Collateral Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D006497:Heparan Sulfate / Q000494:pharmacology; D007273:Injections, Intramuscular; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins; D012685:Sepharose / Q000031:analogs & derivatives / Q000494:pharmacology; D013552:Swine
D000345:Affinity Labels; D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D011994:Recombinant Proteins; D012685:Sepharose; C037405:heparin-sepharose