XXXX activation is necessary for ischemic preconditioning in @entity1184 myocardium.

@entity22943 @entity63 @entity1184 @entity1283 @entity12001 @entity13720 @entity35
The JAK-STAT pathway is activated in the early and late phases of ischemic preconditioning (IPC) in normal myocardium. The role of this pathway and the efficacy of IPC in @entity1184 hearts remain largely unknown. We hypothesized that phosphorylated @entity12001 (pSTAT-3) is necessary for effective IPC in pressure-overload @entity1184 . Male @entity35 8 wk after thoracic aortic constriction (TAC) or sham operation underwent echocardiography and Langendorff perfusion. Randomized hearts were subjected to 30 min of global @entity63 and 120 min of reperfusion with or without IPC in the presence or absence of the @entity13720 inhibitor @entity22943 (AG). Functional recovery and STAT activation were assessed. TAC @entity35 had a 31% increase in left ventricular mass (1,347 +/- 58 vs. 1,028 +/- 43 mg, TAC vs. sham, P < 0.001), increased anterior and posterior wall thickness but no difference in ejection fraction compared with sham-operated @entity35 . In TAC, IPC improved end-reperfusion maximum first derivative of developed pressure (+dP/dt(max); 4,648 +/- 309 vs. 2,737 +/- 343 mmHg/s, IPC vs. non-IPC, P < 0.05) and minimum -dP/dt (-dP/dt(min); -2,239 +/- 205 vs. -1,215 +/- 149 mmHg/s, IPC vs. non-IPC, P < 0.05). IPC increased nuclear pSTAT-1 and pSTAT-3 in sham-operated @entity35 but only pSTAT-3 in TAC. AG in TAC significantly attenuated +dP/dt(max) (4,648 +/- 309 vs. 3,241 +/- 420 mmHg/s, IPC vs. IPC + AG, P < 0.05) and -dP/dt(min) (-2,239 +/- 205 vs. -1,323 +/- 85 mmHg/s, IPC vs. IPC + AG, P < 0.05) and decreased only nuclear pSTAT-3. In @entity1283 , JAK-STAT signaling is important in IPC and exhibits a pattern of STAT activation distinct from nonhypertrophied myocardium. Limiting @entity12001 activation attenuates the efficacy of IPC in @entity1184 .
