Apoptosis contributes to myocardial cell death after cardiac ischemia and reperfusion. Using beta-actin Daxx-DN transgenic mice, we have previously shown that Daxx, a Fas-associated protein, is involved in apoptotic cell death in myocardial reperfusion injury.
The aim of our study was to better characterize Daxx-DN cardioprotective properties during ischemia/reperfusion (IR) injury.
Material and Methods
Daxx-DN (+/-) versus wild-type (WT) mice were subjected to a postconditioning protocol (PostC) in a surgical model of myocardial IR. 9 Daxx-DN and 12 WT mice underwent a PostC protocol comprising, after 40 minutes of left coronary artery occlusion, 3 cycles of 1-minute reperfusion and 1-minute reocclusion before the 60 minutes of reperfusion. Results were compared to those obtained in mice IR Daxx-DN (n=10) and IR WT (n=19) subjected to an IR protocol (ischemia: 40 minutes of - reperfusion: 60 minutes). An additional group of PreC WT mice (n=7) were subjected to the same algorithm than PostC but applied 10 minutes before ischemia. Determination of area at risk and infarct size (Inf/AR) was assessed by dual staining by triphenyltetrazolium chloride and phtalocyanine blue dye. DNA fragmentation as a marker of apoptosis was quantified in ischemic versus non ischemic parts of left ventricles at the end of surgery. Comparisons between groups were assessed by one-way or two-way ANOVA and statistical significance was defined as a value P<0.05.
Area at risk was comparable among groups (p=ns). Interestingly, infarct size was significantly reduced both in PostC WT and PostC Daxx-DN mice versus IR WT and IR Daxx-DN, respectively (p<0.0001). The cardioprotective effect offered by PostC was as efficient as PreC (p=ns). DNA fragmentation was decreased in the ischemic part of PostC Daxx-DN and PostC WT when compared to the non ischemic part taken as control.
This study shows that Daxx-DN hearts are sensitive to postconditioning in vivo and that the efficiency of cardioprotection upon postconditioning is maximal compared to the Daxx-DN transgene-induced cardioprotection. This suggests either that postconditioning induces a maximal activation of the underlying mechanisms involved in Daxx-DN cardioprotection or that the postconditioning activates additional specific cellular pathways.Le texte complet de cet article est disponible en PDF.