1. HDL protects against myocardial ischemia reperfusion injury via miR-34b and miR-337 expression which requires STAT3
- Author
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Fabrizio Montecucco, Marie-Claude Brulhart-Meynet, Miguel Frias, Sandrine Lecour, Richard W. James, and Sarah Pedretti
- Subjects
0301 basic medicine ,Critical Care and Emergency Medicine ,Apoptosis ,Cardioprotection ,030204 cardiovascular system & hematology ,Biochemistry ,Vascular Medicine ,STAT3 ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,High-density lipoprotein ,Animal Cells ,Ischemia ,Medicine and Health Sciences ,Small interfering RNAs ,Myocytes, Cardiac ,High-density lipoproteins ,Phosphorylation ,Hypoxia ,ddc:616 ,Cardiomyocytes ,Multidisciplinary ,biology ,Heart ,3. Good health ,Nucleic acids ,Medicine ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,Anatomy ,Cellular Types ,MiRNA ,Lipoproteins, HDL ,Research Article ,Signal Transduction ,STAT3 Transcription Factor ,medicine.medical_specialty ,Cell Survival ,Science ,Muscle Tissue ,Myocardial Reperfusion Injury ,03 medical and health sciences ,Extraction techniques ,In vivo ,Internal medicine ,medicine ,Genetics ,Animals ,Humans ,Viability assay ,Non-coding RNA ,Natural antisense transcripts ,Muscle Cells ,Biology and life sciences ,business.industry ,Cell Biology ,Hypoxia (medical) ,medicine.disease ,RNA extraction ,Gene regulation ,Rats ,Research and analysis methods ,MicroRNAs ,030104 developmental biology ,Endocrinology ,Biological Tissue ,chemistry ,Reperfusion ,biology.protein ,Cardiovascular Anatomy ,RNA ,Gene expression ,business ,Reperfusion injury - Abstract
PurposeHigh density lipoprotein (HDL) protects against myocardial infarction via mechanisms that remain unclear. STAT3 (signal transducer and activator of transcription 3) plays a key role in HDL-induced cardioprotection. In the heart, microRNAs (miRNAs) are involved in ischemia reperfusion injury. We therefore investigated whether the cardioprotective effect of HDL modulates miRNAs as a downstream target of STAT3 activation.MethodsSTAT3 cardiomyocyte deficient mice (STAT3-KO) and wildtype littermates (STAT3-WT) were submitted to left coronary ligature and reperfused (IR) with or without injection of HDL. Infarct size (IS) was determined and cardiac miRNA expression was evaluated after reperfusion in sham, IR and IR+HDL hearts by microarray analysis. In vitro, neonatal rat ventricular cardiomyocytes were submitted to hypoxia with or without HDL incubation. Cell viability and miRNA expression were analysed.ResultsIn vivo, HDL reduced IS from 40.5±4.3% to 24.4±2.1% (pConclusionsOur study, performed both in vivo and in vitro, delineates a novel cardioprotective signalling pathway activated by HDL, involving STAT3-mediated decrease of miR-34b and miR-337 expression.
- Published
- 2019