Therapeutic angiogenesis using naked DNA expressing two isoforms of the hepatocyte growth factor in a porcine acute myocardial infarction model.
OBJECTIVE
We evaluated the potency of therapeutic angiogenesis using intramyocardial injection of naked DNA expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in a porcine myocardial infarction model.


METHODS
Four weeks after left anterior descending coronary artery ligation, 14 pigs were allocated to pCK-Null (negative control, n=7) or pCK-HGF-X7 (n=7) treatment groups. Gated myocardial single photon emission computed tomography was performed 4 and 8 weeks following coronary ligation. The effect of pCK-HGF-X7 on capillary density in the gene-injected myocardium was examined by histological analysis using alkaline phosphatase staining.


RESULTS
Segmental myocardial perfusion of the underperfused area (< or =70%) from coronary ligation increased in the pCK-HGF-X7 group (p=0.051), without significant differences in changes over time between the two groups (p=0.54). Systolic wall thickening (p=0.001), left ventricular end-diastolic (p=0.045) and end-systolic volumes (p=0.009), and left ventricular ejection fraction (p=0.041) changed in both groups without significant differences in changes over time between the two groups. The increase in the left stoke volume was higher in the pCK-HGF-X7 group than in the pCK-Null group (p=0.008). Histological analysis showed that capillary density was significantly higher in the pCK-HGF-X7 group than the pCK-Null group (p<0.001).


CONCLUSIONS
Intramyocardial injection of pCK-HGF-X7 induced significant angiogenesis at infarct-border zone, and increased the left ventricular stroke volume probably caused by reverse remodeling process.
Cho
Kwang Ree
KR
Department of Thoracic and Cardiovascular Surgery, Cheju Halla General Hospital, Republic of Korea.
Choi
Jae-Sung
JS
Hahn
Woong
W
Kim
Dong Sik
DS
Park
Jin Sik
JS
Lee
Dong Soo
DS
Kim
Ki-Bong
KB
D000818:Animals; D002196:Capillaries / Q000473:pathology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D010957:Plasmids; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013318:Stroke Volume; D034421:Sus scrofa; D015899:Tomography, Emission-Computed, Single-Photon
D020033:Protein Isoforms; D017228:Hepatocyte Growth Factor