AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 284: H2351-H2359, 2003; doi:10.1152/ajpheart.00783.2002
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Vol. 284, Issue 6, H2351-H2359, June 2003

Bax ablation protects against myocardial ischemia-reperfusion injury in transgenic mice

Edith Hochhauser1, Shaye Kivity1, Daniel Offen2, Nilanjana Maulik4, Hajime Otani4, Yael Barhum2, Hannah Pannet2, Vladymir Shneyvays3, Asher Shainberg3, Valeri Goldshtaub1, Anna Tobar1, and Bernardo A. Vidne1

1 Cardiac Research Laboratory, Department of Cardiothoracic Surgery, and 2 Neurosciences Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Tel Aviv University, Tel Aviv 69978; 3 Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel; and 4 Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1110

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 labeling-positive 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.

Bax-deficient hearts; heart; apoptosis


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