Abstract P077: Ischemic Preconditioning Improves Postischemic Cardiac Function by Preserving PTEN Activity
Background Ischemic preconditioning (IPC) increases post-ischemic functional recovery. Although reduced infarct size is associated with the better outcome, its underlying mechanism is not fully understood. The phosphatase and tensin homologue deleted on chromosome ten (PTEN) promotes cell death and increases myocardial contractility. We recently reported that IPC attenuates loss of PTEN activity in post-ischemic hearts. In the present study, we have investigated the hypothesis that IPC improves post-ischemic cardiac function by preserving PTEN activity.
Methods and Results Isolated mouse hearts were exposed to no ischemia as control (CON) or IPC, consisting of 10-min ischemia and 5-min reperfusion (I-10/R-5), followed by I-30/R-120. bpV(phen) (10 µM), a PTEN inhibitor, or vehicle was added into the perfusion line in IPC group following reperfusion. Isolated hearts from muscle-specific PTEN knockout mice (Ptenloxp/loxp;ckm+/−) and control mice (Ptenloxp/loxp;ckm−/−) were exposed to I-30/R-30. Left ventricular (LV) pressure was monitored by a pressure catheter. Myocardial infarct size was measured by triphenyltetrazolium chloride staining. After I-30/R-120, IPC increased LV developed pressure (LVDP) and maximal +dp/dt (+dp/dtm) compared with CON. bpV blocked the effects of IPC (LVDP: 42±4 vs. 63±4 mmHg, p<0.01; +dp/dtm: 1209±101 vs. 1880±155 mmHg/sec, p<0.01). However, it did not increase infarct size compared with vehicle. Muscle-specific PTEN knockout modestly decreased LVDP and +dp/dtm in isolated perfused hearts under basal conditions, but it markedly impaired their recovery after I-30/R-30 compared with control (LVDP: 21±4 vs. 45±5 mmHg, p<0.01; +dp/dtm: 784±146 vs. 1795±154 mmHg/sec, p<0.01). Myocardial infarct size was decreased in PTEN knockout hearts after I/R.
Conclusions: PTEN inhibition blocks the improvement of cardiac functional recovery induced by IPC. Loss of PTEN exacerbates post-ischemic dysfunction in isolated hearts. Therefore, our studies suggest that IPC attenuates post-ischemic cardiac dysfunction by preserving PTEN activity.
- © 2011 by American Heart Association, Inc.