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

Autor: Mansoureh Eghbali, Negar Motayagheni, Gregoire Ruffenach, Neusha Barakai, Jingyuan Li, Vera Regitz-Zagrosek, Soban Umar, Christine M. Cunningham, Georgios Kararigas
Rok vydání: 2017
Předmět:
0301 basic medicine
Time Factors
Caveolin 2
030204 cardiovascular system & hematology
Mitochondrial Membrane Transport Proteins
Mitochondria
Heart
Mice
chemistry.chemical_compound
0302 clinical medicine
Bolus (medicine)
Pregnancy
Cluster Analysis
Myocardial infarction
Phosphorylation
Phospholipids
chemistry.chemical_classification
MPTP
Anesthesia
Emulsions
Female
Cardiology and Cardiovascular Medicine
Protein Binding
Signal Transduction
Polyunsaturated fatty acid
STAT3 Transcription Factor
medicine.medical_specialty
Ischemia
chemistry.chemical_element
Myocardial Reperfusion Injury
Calcium
Protective Agents
Article
Permeability
03 medical and health sciences
Internal medicine
medicine
Animals
Molecular Biology
GSK3B
Glycogen Synthase Kinase 3 beta
Mitochondrial Permeability Transition Pore
business.industry
Gene Expression Profiling
medicine.disease
Rats
Soybean Oil
Disease Models
Animal
030104 developmental biology
Endocrinology
chemistry
Transcriptome
business
Reperfusion injury
Zdroj: Journal of Molecular and Cellular Cardiology. 102:108-116
ISSN: 0022-2828
DOI: 10.1016/j.yjmcc.2016.11.006
Popis: 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.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, p0.01). 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, p0.01) and significantly increased phosphorylation of STAT3 (1.8±0.08 vs. 1±0.16 in CTRL, p0.05) and GSK-3β (2.63±0.55 vs. 1±0.0.34 in CTRL, p0.05). 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.ITLD protects the heart in late pregnancy against I/R injury by inhibiting the mPTP opening through Cav2/STAT3/GSK-3β pathway.
Databáze: OpenAIRE
Externí odkaz: