Elevated DNase activity and caspase expression in association with apoptosis in failing ischemic sheep left ventricles

We examined the DNase activity as well as the expression of the caspases in left ventricles of failing sheep hearts and compared it with samples from normal controls. The sheep model of chronic ischemic heart failure was deve loped by intracoronary micro-embolisation. Moderate heart failure was defin ed as a decrease of left ventricular (LV) ejection fraction (EF) to 35% or less and was stable for four weeks after the last embolisation. The failing hearts were harvested from these animals six months later. Bovine pancreas DNase I was used as a standard for the DNase zymograms. In normal sheep le ft ventricles, a low level of the DNase I-like activity was detected (1.16 +/- 0.17 pg/100 mu g protein, n = 20), whereas it was elevated (3.64 +/- 0. 49 pg/100 mu g, n = 32, p < 0.001) in the ischemic failing LV samples. The identity of the DNase in sheep is yet to be fully characterised. However, w e also detected the expression of caspase-2 and caspase-3 by Western blotti ng. There was a 2.2-fold increased expression of caspase-2 p < 0.001= and a 2.6-fold increased expression of caspase-3 p < 0.001) in failing left vent ricles compared to normal samples.