Abstract 222: Intralipid-induced Cardioprotection In Late Pregnancy Is Fully Abolished By Inhibition Of Stat3, But Not Pi3k Signaling Pathway

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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. Here we explored the therapeutic potential of Intralipid (ITLD) in the protection of LP hearts against I/R injury, and investigate the involvement of the signal transducer and activator of transcription-3 (STAT3) and phosphoinositide 3-kinase (PI3K) signaling pathways in ITLD-induced cardioprotetion. Isolated LP mouse hearts were subjected to 20 min ischemia followed by 40 min 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). The heart function and the infarct size were measured. The Intralipid-induced cardioprotection was fully abolished by Stattic, as RPP was significantly lower in the presence of Stattic (RPP=8881±1331 mmHg*beats/min vs. 1186±563 mmHg*beats/min in ITLD+Stattic, p<0.01) at the end of reperfusion. In fact, all of the hemodynamic indexes in ITLD+Stattic were not significantly different from CTRL. The infarct size was also significantly larger in ITLD+Stattic group when compared to Intralipid alone (47.9±2.5% in ITLD+Stattic vs. 21.7±2.6 % in ITLD, p<0.01). The Intralipid-induced cardioprotection was only partially abolished by LY294002, as at the end of 40 min reperfusion the RPP was significantly lower 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; RPP=5212±1955 mmHg*beats/min in ITLD+LY vs.1186±563 mmHg*beats/min in ITLD+Stattic, p<0.05). The infarct size was also larger 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%, p<0.05). In conclusion, Intralipid protects the late pregnant heart against I/R injury via the STAT3 rather than the PI3K signaling pathway.

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