HDL protects against myocardial ischemia reperfusion injury via miR-34b and miR-337 expression which requires STAT3
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ABSTRACT:
ORGANISM(S): Mus musculus synthetic construct
PROVIDER: GSE124176 | GEO | 2019/06/25
REPOSITORIES: GEO
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Project description: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% (p<0.05) in STAT3-WT mice. HDL failed to protect in STAT3-KO mice. In STAT3-WT mice, both miR-34b and miR-337 were increased in IR compared to sham and IR+HDL groups (p<0.05). These miRNAs were not modulated in STAT3-KO mice. In vitro, incubation with HDL improved cell viability against hypoxia (p<0.05). The expression of miR-34b and miR-337 was increased by hypoxia and reduced by HDL treatment (p<0.05). In cardiomyocytes transfected with miRNA mimics, HDL failed to improve cell viability against hypoxia.ConclusionsOur 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.
| S-EPMC6586303 | biostudies-literature
Project description:HDL protects against myocardial ischemia reperfusion injury via miR-34b and miR-337 expression which requires STAT3
| PRJNA510950 | ENA
Project description:HDL proteome dynamics may determine HDL cardioprotective functions. We aimed to characterize proteome and lipid profiles in small, medium and large (S/M/L) HDL fractions and analyze their functions. We characterized mouse HDL fractions by their high phospholipid (PL) content and collected S/M/L-HDLsubfractions by using fast protein liquid chromatography. The pooled S/L/M-HDL elution was subjected to mass spectrometry (MS) analysis using a Qstar XL-MS system, performing HDL subpopulation proteomic analysis. Fifty-one HDL proteins (39 in S-HDL, 27 in M-HDL and 29 in L-HDL) were identified and grouped into 4 functional categories (5 in lipid metabolism, 24 in immune response, 7 in coagulation, and 14 others). There were 16, 3 and 7 proteins present in only the S-HDL, M-HDL and L-HDL subfractions, respectively, and 11 proteins overlapped in all S/M/L-HDL subfractions. The dynamic changes in relative HDL protein levels were then characterized based on their functional groups by biological and bioinformatical methods.
2019-11-12 | PXD011185 | Pride
Project description:miRNAs and other small RNAs have been found associated with high-density lipoproteins (HDL). The aim of this study was to investigate the miRNA signature on human HDL from 10 donors.
2019-01-03 | GSE124559 | GEO
Project description:We quantified differential gene (mRNA) expression in human coronary artery cells treated with native HDL, reconstituted HDL, lipid-free apolipoprotein A-I, small unilamellar vesicles, or PBS control. These data were used to determine which genes are regulated by native HDL compared to components of HDL and categorize data based on shared sets of genes and distinct sets of genes regulated by each component.
2014-02-27 | GSE53201 | GEO
Project description:Background: High density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that it might also inhibit atherogenesis by combating inflammation. Methods and Results: To identify potential anti-inflammatory mechanisms, we challenged macrophages with lipopolysaccharide (LPS), an inflammatory microbial ligand for Toll-like receptor 4 (TLR4). HDL inhibited the expression of 33% (301 of 911) of the genes normally induced by LPS, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by TLR4 and the TRAM/TRIF signaling pathway. Unexpectedly, HDL’s ability to inhibit gene expression was independent of cellular cholesterol stores. Moreover, it was unaffected by downregulation of two ATP-binding cassette transporters, ABCA1 and ABCG1, that promote cholesterol efflux. To examine the pathway’s potential in vivo relevance, we used mice deficient in apolipoprotein (apo) A-I, HDL’s major protein. After infection with Salmonella (a Gram-negative bacterium that expresses LPS), apoA-I–deficient mice had 6-fold higher plasma levels of interferon-beta-a key regulator of the type I interferon response than did wild-type mice. Conclusions: HDL inhibits a subset of LPS-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection. 12 arrays, 3 experimental groups, mMncN (no treatment), mMncL (LPS treated, exposed for 4 h to serum-free medium or serum-free medium supplemented with 100 ng/mL of LPS), and mMwtL (HDL treated, Macrophages were treated for 4 h with serum-free medium or serum-free medium supplemented with 50 mg/mL of HDL, washed twice with PBS).
2010-10-01 | E-GEOD-19340 | biostudies-arrayexpress
Project description:miRNAs are exported to high density lipoproteins (HDL). This study aimed to understand what miRNAs are exported from primary islets to HDL in vitro.
2019-01-16 | GSE125136 | GEO
Project description:The aim of this study was to identify HDL and apoE-regulated genes in human placental endothelial cells (HPEC), which are exposed to fetal HDL. HPECs extracted from 5 human placentas were cultivated and treated for 16 h with 15ug/ml fetal HDL, 15ug/ml reconstituted HDL (rHDL), or endothelial basal medium (EBM) as vehicle control. Gene expression analysis from these 3 conditions (5 biological replicates) using 15 Applied Biosystems Human Whole Genome Survey V2.0 Microarrays was perfomed and significantly differentially expressed genes between two different groups (HDL vs control or rHDL vs control) were identified.
2011-09-01 | E-MEXP-3299 | biostudies-arrayexpress
Project description:We quantified differential microRNA (miRNA) expression in human coronary artery cells treated with native HDL, reconstituted HDL, lipid-free apolipoprotein A-I, small unilamellar vesicles, or PBS control. These data were used to determine whichmiRNAs are regulated by native HDL compared to components of HDL and categorize data based on shared sets of miRNAs and distinct sets of miRNAs regulated by each component.
2014-02-27 | GSE53315 | GEO
Project description:The lungs are highly susceptible to injury, including ischemia/reperfusion (I/R) injury. Pulmonary I/R injury can occur when correcting conditions such as primary pulmonary hypertension, and is also relatively common after lung transplantation or other cardiothoracic surgery. Methods to reduce pulmonary I/R injury are urgently needed to improve outcomes following procedures such as lung transplantation. Remote liver ischemic preconditioning (RLIPC) is an effective cardioprotective measure, reducing damage caused by subsequent cardiac I/R injury, but little is known about its potential role in pulmonary protection. Here, we analyzed the efficacy and mechanistic basis of RLIPC in a rat model of pulmonary I/R injury. RLIPC reduced lung I/R injury, lessening structural damage, inflammatory cytokine production and apoptosis. In addition, RLIPC preserved pulmonary function compared to controls following lung I/R injury. RLIPC stimulated phosphorylation of pulmonary STAT3, a component of the SAFE signaling pathway, but not phosphorylation of RISK pathway signaling proteins. Accordingly, STAT3 inhibition using AG490 eliminated the pulmonary protection afforded by RLIPC. Our data demonstrate for the first time that RLIPC protects against pulmonary I/R injury, via a signaling pathway requiring STAT3 phosphorylation.
| S-EPMC5955491 | biostudies-literature