Angiogenic effects of dual gene transfer of bFGF and PDGF-BB after myocardial infarction.
Therapeutic effects of combination of angiogenic growth factors for the treatment of ischemia after myocardial infarction are largely unknown. Plasmids expressing basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF-BB) or their combination with a 1:1 mass ratio were injected into hearts with 7-day-old myocardial infarction. Hearts were harvested after 1 and 4 weeks after gene transfer. The major findings in this chronic myocardial infarction model were that bFGF, PDGF-BB and their combination all had a more pronounced angiogenic effect on the arteriolar than the capillary level. bFGF stimulated both capillary and arteriolar growth while PDGF-BB preferentially stimulated arterioles. The combination increased the amount of both capillaries and arterioles and in addition gave rise to stable capillaries compared to single factor transfer but did not further enhance angiogenesis. No cardiovascular side effects were observed after gene transfer.
Department of Cardiology, Karolinska Institutet, Huddinge University Hospital, Stockholm SE-141 86, Sweden.
X
X
Hao
A
A
Månsson-Broberg
T
T
Gustafsson
K H
KH
Grinnemo
P
P
Blomberg
A J
AJ
Siddiqui
E
E
Wärdell
C
C
Sylvén
D000818:Animals; D001160:Arterioles / Q000502:physiology; D002196:Capillaries / Q000502:physiology; D004195:Disease Models, Animal; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009203:Myocardial Infarction / Q000235:genetics* / Q000628:therapy; D018919:Neovascularization, Physiologic / Q000235:genetics; D009929:Organ Size; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology
D016222:Fibroblast Growth Factor 2; D017479:Receptors, Platelet-Derived Growth Factor