Abstract 331: Activation of the Safe Pathway Against Cardiac Ischemia-Reperfusion Injury Goes Beyond the Risk Pathway in the Late Pregnancy
Introduction: We have recently shown that the heart of late pregnant (LP) rodent is more prone to ischemia/reperfusion (I/R) injury compared to non-pregnant. We also reported that post-ischemic adminstartion of (ITLD) protects the LP hearts against I/R injury. Here we investigated Survivor Activating Factor Enhancement (SAFE) pathway, which requires the activation of the signal transducer and activator of transcription 3 (STAT-3) and it can successfully lessen cardiomyocyte death at the time of reperfusion, independently of the activation of the already well-described Reperfusion Injury Salvage Kinase (RISK) pathway (which includes activation of phosphoinositide 3-kinase (PI3K) signaling pathways) in ITLD-induced cardioprotetion.
Methods: Isolated LP mouse hearts were subjected to 20 min ischemia followed by 40 reperfusion with 1) Krebs Henseleit buffer (CTRL group), 2) 1% intralipid (ITLD group) or 3) ITLD+STAT3 inhibitor Stattic (20 μM, Stattic group), and 4) ITLD+PI3K inhibitor LY294002 (45 μM). Hemodynamics and myocardial infarction were measured. Two-way and one-way ANOVA was used for statistical analysis. The data are from four to six mice in each group. P<0.05 was considered statistically significant. Values are expressed as mean± SE.
Results: The Intralipid-induced cardioprotection was only partially abolished by PI3K inhibitor, LY294002, whereas it was fully abolished when stattic was applied at the end of 40 min reperfusion. The RPP was significantly lower in LY294002 treated group compared to the group treated with Intralipid alone, but still significantly higher than ITLD+Stattic: RPP=8881±1331 mmHg*beats/min in ITLD vs. 5212±1955 mmHg*beats/min in ITLD+LY, p<0.05; 1186±563 mmHg*beats/min in ITLD+Stattic vs. 5212±1955 mmHg*beats/min in ITLD+LY, p<0.05. The infarct size was also larger in LY294002 treated group when compared to Intralipid alone (32.8±3.1% in ITLD+LY vs. 21.7±2.6% in ITLD, p<0.05), but lower than ITLD+Stattic group (32.8±3.1% in ITLD+LY vs 47.9±2.5% ITLD+Stattic, p<0.05).
Conclusion: Intralipid protects the heart of late pregnant mice against I/R injury mainly through SAFE-STAT3 pathway.
Author Disclosures: J. Li: None. M. Eghbali: None.
- © 2014 by American Heart Association, Inc.