Effects of erythropoietin on angiogenesis after myocardial infarction in porcine.
Erythropoietin (EPO) has recently been shown to confer cardioprotective effects via angiogenesis and antiapoptosis. The administration of EPO after myocardial infarction (MI) reduces infarct size and improves cardiac function in small animals. The purpose of this study is to investigate the protective effects of EPO in porcine MI. Each animal in the EPO group received four injections of recombinant human EPO (rhEPO; 6000 U per injection) at 2-day intervals, starting after coronary occlusion. Animals in the control group received saline. Left ventriculography was performed just after coronary occlusion and at 28 days. Time-course changes in serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and fibroblast growth factor (FGF) were measured. The number of vessels was calculated, and the mRNA expressions of VEGF and insulin-like growth factor (IGF) were examined. Left ventricular function was similar between the groups. The numbers of cells positive for anti-α-smooth muscle actin, von Willebrand factor, and c-kit were significantly higher in the EPO group than in the controls (P < 0.05). The EPO group exhibited significantly higher HGF and FGF concentrations (P < 0.05) and higher expression of VEGF and IGF mRNA (P < 0.05) compared with the controls. In conclusion, EPO accelerates angiogenesis via the upregulation of systemic levels such as HGF and FGF, and the local expression of VEGF and IGF, in porcine MI.
Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, Kanagawa, 227-8501, Japan.
Keisuke
K
Kawachi
Yoshitaka
Y
Iso
Takatoshi
T
Sato
Kohei
K
Wakabayashi
Youichi
Y
Kobayashi
Youichi
Y
Takeyama
Hiroshi
H
Suzuki
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013002:Somatomedins / Q000235:genetics; D013318:Stroke Volume; D034421:Sus scrofa; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics; D016277:Ventricular Function, Left
D043925:Angiogenesis Inducing Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013002:Somatomedins; D042461:Vascular Endothelial Growth Factor A; C103998:epoetin beta; D004921:Erythropoietin; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor