Protein and angiogenic dose-response expression of phVEGF-A(165) gene in rat myocardium.
Therapeutic myocardial angiogenesis by means of transient overexpression of angiogenic growth factors is a potential treatment modality for severe ischemic heart disease. This study was undertaken in the rat to examine effects of phVEGF-A(165) myocardial transfection in terms of dose-response as regards the number of hVEGF-A expressing cells on one hand and on the other angiogenesis. Non-surgical echocardiography-guided intramyocardial injection of phVEGF-A(165) was done into normoxic or hypoxic (10% O(2)) rats. Cardiomyocytes expressing VEGF-A protein, capillary morphology and density were determined after 5 days. VEGF protein expression was seen in rat cardiomyocytes located around the tip of the injection scar and increased dose-dependently (p<0.05). Microvessel density also increased dose-dependently with phVEGF(165) (p<0.05) and with hypoxia (p<0.05). No vascular tumours were observed. In conclusion, direct intramyocardial injection of phVEGF-A(165) in the rat results in a dose-dependent increase both in transfected hVEGF-A protein producing cells and in angiogenesis.
Sylvén
C
C
Department of Cardiology, Huddinge University Hospital, Karolinska Institute, Novum SE-141 86 Stockholm, Sweden. christer.sylven@medhs.ki.se
Sarkar
N
N
Wärdell
E
E
Jämsä
A
A
Drvota
V
V
Blomberg
P
P
Bin Islam
K
K
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D000860:Hypoxia / Q000628:therapy; D007273:Injections, Intramuscular; D008297:Male; D017202:Myocardial Ischemia / Q000628:therapy; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A
D016228:Endothelial Growth Factors; D042461:Vascular Endothelial Growth Factor A