Bcl-xL gene transfer protects the heart against ischemia/reperfusion injury.
Ischemia and reperfusion (I/R) injury causes the progression of cardiac dysfunction. The prevention of cardiomyocyte-loss due to I/R injury is important for the treatment of heart failure. Therefore, we employed antiapoptotic Bcl-xL protein to prevent I/R injury in the heart and evaluated the cardioprotective effect of Bcl-xL transduction by adenoviral vector (Adv) after I/R injury. Adv with Bcl-xL gene was injected in the rat heart 4 days prior to I/R. The prevention of cardiac performance-loss and the reduction of cardiac apoptosis, after 30min ischemia and 30min reperfusion of global I/R, were demonstrated in the heart with adenoviral Bcl-xL transduction. Also, significant reductions of the infarct size and serum creatine kinase levels were observed in the heart transduced with Bcl-xL gene compared with control after 30min ischemia and 24h reperfusion of the left anterior coronary artery. Thus, Bcl-xL may serve as a potential therapeutic tool for cardioprotection.
Huang
Jianhua
J
Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan.
Ito
Yoshinori
Y
Morikawa
Masayuki
M
Uchida
Hiroaki
H
Kobune
Masayoshi
M
Sasaki
Katsunori
K
Abe
Tomio
T
Hamada
Hirofumi
H
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D014161:Transduction, Genetic / Q000379:methods; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D002316:Cardiotonic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein