TY - JOUR
T1 - Bax ablation protects against myocardial ischemiareperfusion injury in transgenic mice
AU - Hoehhauser, Edith
AU - Kivity, Shaye
AU - Offen, Daniel
AU - Maulik, Nilanjana
AU - Otani, Hajime
AU - Barhum, Yael
AU - Pannet, Hannah
AU - Shneyvays, Vladymir
AU - Shainberg, Asher
AU - Goldshtaub, Valeri
AU - Tobar, Anna
AU - Vidne, Bernardo A.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - The role of the proapototic Bax gene in ischemia-reperfusion (I/R) injury was studied in three groups of mice: homozygotic knockout mice lacking the Bax gene (Bax-/-), heterozygotic mice (Bax+/-), and wild-type mice (Bax+/+). Isolated hearts were subjected to ischemia (30 min, 37°C) and then to 120 min of reperfusion. The left ventricular developed force of Bax-deficient vs. Bax+/+ hearts at stabilization and at 120 min of reperfusion was 1,411 ± 177 vs. 1,161 ± 137 mg and 485 ± 69 vs. 306 ± 68 mg, respectively. Superior cardiac function of Bax-/- hearts after I/R was accompanied by a decrease in creatine kinase release, caspase 3 activity, irreversible ischemic injury, and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelingpositive cardiomyocytes. Electron microscopic evaluation revealed reduced damage to mitochondria and the nuclear chromatin structure in Bax-deficient mice. In the Bax+/- hearts, the damage markers were moderate. The superior tolerance of Bax knockout hearts to I/R injury recommends this gene as a potential target for therapeutic intervention in patients with severe and intractable myocardial ischemia.
AB - The role of the proapototic Bax gene in ischemia-reperfusion (I/R) injury was studied in three groups of mice: homozygotic knockout mice lacking the Bax gene (Bax-/-), heterozygotic mice (Bax+/-), and wild-type mice (Bax+/+). Isolated hearts were subjected to ischemia (30 min, 37°C) and then to 120 min of reperfusion. The left ventricular developed force of Bax-deficient vs. Bax+/+ hearts at stabilization and at 120 min of reperfusion was 1,411 ± 177 vs. 1,161 ± 137 mg and 485 ± 69 vs. 306 ± 68 mg, respectively. Superior cardiac function of Bax-/- hearts after I/R was accompanied by a decrease in creatine kinase release, caspase 3 activity, irreversible ischemic injury, and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelingpositive cardiomyocytes. Electron microscopic evaluation revealed reduced damage to mitochondria and the nuclear chromatin structure in Bax-deficient mice. In the Bax+/- hearts, the damage markers were moderate. The superior tolerance of Bax knockout hearts to I/R injury recommends this gene as a potential target for therapeutic intervention in patients with severe and intractable myocardial ischemia.
KW - Apoptosis
KW - Bax-deficient hearts
KW - Heart
UR - http://www.scopus.com/inward/record.url?scp=17344375146&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00783.2002
DO - 10.1152/ajpheart.00783.2002
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C2 - 12742833
AN - SCOPUS:17344375146
SN - 0363-6135
VL - 284
SP - H2351-H2359
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6 53-6
ER -