Abstract
Preconditioning (PC) protects against ischemia-reperfusion (I/R) injury via the activation of the JAK-STAT pathway. We hypothesized that the mediators responsible for PC can be transferred to naive myocardium through the coronary effluent. Langendorff-perfused hearts from male Sprague-Dawley rats were randomized to paired donor/acceptor protocols with or without PC in the presence or absence of the JAK-2 inhibitor AG-490 (n = 6 for each group). Warmed, oxygenated coronary effluent collected during the reperfusion phases of PC (3 cycles of 5 min ischemia and 5 min reperfusion) was administered to acceptor hearts. The hearts were then subjected to 30 min ischemia and 40 min reperfusion. The left ventricles were analyzed for phosphorylated (p)STAT-1, pSTAT-3, Bax, Bcl, Bcl-XL/Bcl-2-associated protein (BAD), and caspase-3 expression by Western blot. A separate group of hearts (n = 6) was analyzed for STAT activation immediately after the transfer of the PC effluent (no I-R). Baseline cardiodynamics were not different among the groups. End-reperfusion maximal change in pressure over time (+dP/dtmax) was significantly (P < 0.05) improved in acceptor PC (3,637 ± 199 mmHg/s) and donor PC (4,304 ± 347 mmHg/s) hearts over non-PC donor (2,020 ± 363 mmHg/s) and acceptor (2,624 ± 345 mmHg/s) hearts. Similar differences were seen for minimal change in pressure over time (-dP/dt min). STAT-3 activation was significantly increased in donor and acceptor PC hearts compared with non-PC hearts. Conversely, pSTAT-1 and Bax expression was decreased in donor and acceptor PC hearts compared with non-PC hearts. No differences in Bcl,_BAD, or caspase-3 expression were observed. Treatment with AG-490 attenuated the recovery of ±dP/dt in acceptor PC hearts and significantly reduced pSTAT-3 expression. The PC coronary effluent activates JAK-STAT signaling, limits apoptosis, and protects myocardial performance from I/R injury.
Original language | English (US) |
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Pages (from-to) | H257-H262 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 294 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2008 |
Keywords
- Apoptosis
- Cardiac ischemia
- Ischemia-reperfusion injury
- Signal transducers and activators of transcription-3
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)