Bcl-xL gene transfer inhibits Bax translocation and prolongs cardiac cold preservation time in rats.
BACKGROUND
Apoptosis is an important cause of early graft loss after heart transplantation. Bcl-xL was reported to protect the heart against normothermic ischemia and reperfusion injury. In this study, we determined whether overexpression of Bcl-xL could inhibit tissue injury resulting from prolonged cold preservation followed by warm reperfusion of heart transplants.


RESULTS
Lewis rat hearts were transduced with an adenovirus vector harboring Bcl-xL cDNA (AxCAhBclxL) 4 days before collection of tissue. After preservation in University of Wisconsin solution at 4 degrees C for 24 hours, the heart was either perfused with a Langendorff device ex vivo or used for heterotopic heart transplantation in vivo. Bcl-xL gene transfer significantly reduced the infarct size (23.0+/-2.6% versus 47.7+/-7.0% in saline control and 48.6+/-6.1% in vector control, P<0.01) after 2-hour reperfusion at 37 degrees C with the Langendorff device and significantly decreased creatine kinase release (0.82+/-0.27 IU, versus 1.57+/-0.33 and 1.50+/-0.37 IU in saline and vector controls, respectively; P<0.05). In heart transplantation, overexpression of Bcl-xL inhibited Bax translocation from the cytosol to the mitochondria, resulting in decreased cytochrome c release from the mitochondria; it also significantly decreased cardiac cell apoptosis and improved graft survival rate after long cold preservation, followed by warm reperfusion.


CONCLUSIONS
Bcl-xL gene transfer inhibited the translocation of Bax and prolonged the cold preservation time of cardiac transplants. This may be a potential therapeutic method in clinical practice.
Department of Molecular Medicine, Sapporo Medical University, Sapporo, 060-8556, Japan.
Jianhua
J
Huang
Kiminori
K
Nakamura
Yoshinori
Y
Ito
Takeshi
T
Uzuka
Masayuki
M
Morikawa
Sachie
S
Hirai
Kei
K
Tomihara
Toshihiro
T
Tanaka
Yukari
Y
Masuta
Keiji
K
Ishii
Kazunori
K
Kato
Hirofumi
H
Hamada
D000818:Animals; D017209:Apoptosis; D015925:Cryopreservation; D003600:Cytosol / Q000378:metabolism; D006085:Graft Survival; D006321:Heart; D016027:Heart Transplantation / Q000379:methods*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009926:Organ Preservation; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D014161:Transduction, Genetic; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000037:antagonists & inhibitors*; D051020:bcl-X Protein / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology
C494811:BCL2L1 protein, human; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein