Intralipid protects the heart in late pregnancy against ischemia/reperfusion injury via Caveolin2/STAT3/GSK-3β pathway

Abstract

Background We recently demonstrated that the heart of late pregnant (LP) rodents is more prone to ischemia/reperfusion (I/R) injury compared to non-pregnant rodents. Lipids, particularly polyunsaturated fatty acids, have received special attention in the field of cardiovascular research. Here, we explored whether Intralipid (ITLD) protects the heart against I/R injury in LP rodents and investigated the mechanisms underlying this protection. Methods and Results In-vivo female LP rat hearts or ex-vivo isolated Langendorff-perfused LP mouse hearts were subjected to ischemia followed by reperfusion with PBS or ITLD (one bolus of 5mg/kg of 20% in in-vivo and 1% in ex-vivo). Myocardial infarct size, mitochondrial calcium retention capacity, genome-wide expression profiling, pharmacological inhibition and co-immunoprecipitation were performed. One bolus of ITLD at reperfusion significantly reduced the in-vivo myocardial infarct size in LP rats (23.3±2% vs 55.5±3.4% in CTRL, p<0.01). Postischemic administration of ITLD also protected the LP hearts against I/R injury ex-vivo. ITLD significantly increased the threshold for the opening of the mitochondrial permeability transition pore in response to calcium overload (nmol-calcium/mg-mitochondrial protein: 290±17 vs. 167±10 in CTRL, p<0.01) and significantly increased phosphorylation of STAT3 (1.8±0.08 vs. 1±0.16 in CTRL, p<0.05) and GSK-3β (2.63±0.55 vs. 1±0.0.34 in CTRL, p<0.05). The ITLD-induced cardioprotection was fully abolished by Stattic, a specific inhibitor of STAT3. Transcriptome analysis revealed caveolin 2 (Cav2) was significantly upregulated by ITLD in hearts of LP rats under I/R injury. Co-immunoprecipitation experiments showed that Cav2 interacts with STAT3. Conclusions ITLD protects the heart in late pregnancy against I/R injury by inhibiting the mPTP opening through Cav2/STAT3/GSK-3β pathway.

A Review of Anesthetic Effects on Renal Function: Potential Organ Protection

“…In particular, propofol, a widely used anesthetic, has shown potential as a novel organ-protective agent through its efficient membrane-targeted and cytoprotective effects [4]. This is not surprising since lipid emulsions are major components of propofol, which accumulating data show provide organ protective effects against IR injury in many organs, such as the heart, kidney, liver, and intestines [6-13]. …”

The Importance of Intralipid in Heart Protection: A Brief Review

“…Pyruvate kinase isoform M2 (PKM2), which is known to regulate cell apoptosis in the liver, is a direct target of miR122. The obtained data showed that Pyruvate kinase isoform M2(as a cell apoptosis regulator in the liver) and caspase 3 were 2 targets of miR122 since the expression of Pyruvate kinase isoform M2 and capase-3 in the heats subjected to ischemia/reperfusion injury was significantly lower in intralipid group compared to control group in late pregnancy [17] .…”

Lipid Emulsion, More Than Reversing Bupivacaine Cardiotoxicity: Potential Organ Protection

“…Researchers investigating the effect of miRNA during the administration of Intralipid found that Intralipid was able to affect apoptosis via miRNA (6,(11)(12).…”

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