Effects of erythropoietin on cardiac remodeling after myocardial infarction.
Erythropoietin (EPO) has been suggested to have a cardioprotective effect against ischemia. The purpose of this study was to examine the effects of EPO on cardiac remodeling after myocardial infarction (MI). MI was induced by ligation of the coronary artery in Wistar rats. The rats with MI were randomly divided into untreated MI and two EPO-treated MI groups. EPO was administered subcutaneously by injection once a day for 4 days after MI at 5000 U/kg or 3 times a week for 4 weeks at 1000 U/kg. Five days after MI, EPO prevented the increase in activated caspase 3, matrix metalloproteinase-2, and transcriptional activation of activator protein-1 in non-infarcted myocardium. Four weeks after MI, left ventricular weight, left ventricular end-diastolic pressure, and left ventricular dimension were increased, and ejection fraction and E wave deceleration time were decreased. EPO significantly attenuated this ventricular remodeling and systolic and diastolic dysfunction. In addition, EPO significantly attenuated the interstitial fibrosis and remodeling-related gene expression in non-infarcted myocardium. Furthermore, EPO significantly enhanced angiogenesis and reduced apoptotic cell death in peri-infarcted myocardium. In conclusion, when administered after MI, EPO prevents cardiac remodeling and improves ventricular function with enhanced angiogenesis and reduced apoptosis.
Nishiya
Daisuke
D
Department of Internal Medicine and Cardiology, Osaka City University Medical School, Asahimachi, Japan. ndaisuke@med.osaka-cu.ac.jp
Omura
Takashi
T
Shimada
Kenei
K
Matsumoto
Ryo
R
Kusuyama
Takanori
T
Enomoto
Soichiro
S
Iwao
Hiroshi
H
Takeuchi
Kazuhide
K
Yoshikawa
Junichi
J
Yoshiyama
Minoru
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D004921:Erythropoietin / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects*
D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D004921:Erythropoietin; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D020778:Matrix Metalloproteinase 2