2024
Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia
Huang Y, Chen L, Li L, Qi Y, Tong H, Wu H, Xu J, Leng L, Cheema S, Sun G, Xia Z, McGuire J, Rodrigues B, Young L, Bucala R, Qi D. Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia. JCI Insight 2024, 9: e173240. PMID: 38973609, PMCID: PMC11383372, DOI: 10.1172/jci.insight.173240.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorDevelopment of hypertriglyceridemiaWhite adipose tissueAdipose LPLPAR2 expressionLevels of macrophage migration inhibitory factorElevated plasma TG levelsLPL expressionLipoprotein lipaseIncrease PAR2 expressionPlasma MIF levelsPlasma TG levelsMigration inhibitory factorPalmitic acid dietInhibited Akt phosphorylationMIF levelsLipoprotein lipase geneTG levelsObese humansPlasma TGHypertriglyceridemiaAkt phosphorylationLipid storageInhibitory factorAdipose tissue
2021
Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection
Sharma L, Peng X, Qing H, Hilliard BK, Kim J, Swaminathan A, Tian J, Israni-Winger K, Zhang C, Habet V, Wang L, Gupta G, Tian X, Ma Y, Shin HJ, Kim SH, Kang MJ, Ishibe S, Young LH, Kotenko S, Compton S, Wilen CB, Wang A, Dela Cruz CS. Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection. Journal Of Virology 2021, 96: e01241-21. PMID: 34705554, PMCID: PMC8791255, DOI: 10.1128/jvi.01241-21.Peer-Reviewed Original ResearchConceptsType I interferonType III interferonsI interferonIII interferonsCoronavirus infectionInterferon deficiencyViral clearanceViral loadLung infectionType IHealthy young patientsImproved host survivalHost survivalRole of interferonMurine coronavirus infectionMajor health care threatViral burdenYounger patientsEarly diseaseIntranasal routeInterferon treatmentSublethal infectionEarly treatmentLethal infectionTissue injury
2019
Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome
Yang B, Huang Y, Zhang H, Huang Y, Zhou HJ, Young L, Xiao H, Min W. Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome. Journal Of Molecular And Cellular Cardiology 2019, 138: 291-303. PMID: 31751569, DOI: 10.1016/j.yjmcc.2019.10.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBradycardiaCardiomyopathy, DilatedEnhancer Elements, GeneticHistone DeacetylasesHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMEF2 Transcription FactorsMice, KnockoutMitochondria, HeartModels, BiologicalOxidative StressPhenotypeProtein BindingReactive Oxygen SpeciesRNA, MessengerSick Sinus SyndromeSinoatrial NodeThioredoxinsConceptsSick sinus syndromeSinus syndromeHistone deacetylase 4Lower heart rateHeart rateHCN4 expressionConduction systemSinoatrial nodeNormal heart rateCardiac conduction systemHistone 3 acetylationMitochondrial oxidative stressSinus bradycardiaCardiac functionLox/SyndromeHeart rhythmMyosin heavy chainHistological analysisMiceDeletion miceOxidative stressWhole heartProtein levelsUnderlying mechanismCardiomyocyte d-dopachrome tautomerase protects against heart failure
Ma Y, Su KN, Pfau D, Rao VS, Wu X, Hu X, Leng L, Du X, Piecychna M, Bedi K, Campbell SG, Eichmann A, Testani JM, Margulies KB, Bucala R, Young LH. Cardiomyocyte d-dopachrome tautomerase protects against heart failure. JCI Insight 2019, 4: e128900. PMID: 31484822, PMCID: PMC6777911, DOI: 10.1172/jci.insight.128900.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCardiomegalyCytokinesDisease Models, AnimalEchocardiographyGene DeletionGene ExpressionGenetic Predisposition to DiseaseHeart FailureHumansIntramolecular OxidoreductasesMaleMAP Kinase Kinase KinasesMiceMice, Inbred C57BLMice, KnockoutMyocytes, CardiacRecombinant ProteinsSignal TransductionTranscriptomeVascular Endothelial Growth Factor AConceptsTransverse aortic constrictionHeart failureRecombinant DDTConnective tissue growth factor expressionTissue growth factor expressionMore interstitial fibrosisAdvanced heart failureCardiac pressure overloadExperimental heart failureCardiac contractile dysfunctionLittermate control miceSmad-2 activationGrowth factor expressionSarcoplasmic reticulum calcium ATPaseMacrophage migration inhibitory factor (MIF) familyReticulum calcium ATPasePulmonary edemaCardiac dilatationContractile dysfunctionControl miceInterstitial fibrosisPressure overloadAntifibrotic actionAortic constrictionLow VEGF
2016
miR-182 Modulates Myocardial Hypertrophic Response Induced by Angiogenesis in Heart
Li N, Hwangbo C, Jaba IM, Zhang J, Papangeli I, Han J, Mikush N, Larrivée B, Eichmann A, Chun HJ, Young LH, Tirziu D. miR-182 Modulates Myocardial Hypertrophic Response Induced by Angiogenesis in Heart. Scientific Reports 2016, 6: 21228. PMID: 26888314, PMCID: PMC4758045, DOI: 10.1038/srep21228.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiomegalyEndotheliumMechanistic Target of Rapamycin Complex 1Membrane ProteinsMiceMice, KnockoutMicroRNAsMultiprotein ComplexesMyocytes, CardiacNeovascularization, PathologicNitric OxideNitric Oxide Synthase Type IIIProteinsProto-Oncogene Proteins c-aktRGS ProteinsTOR Serine-Threonine KinasesUp-RegulationConceptsHypertrophic responseMiR-182Myocardial hypertrophyEndothelial-cardiomyocyte crosstalkLV pressure overloadEndothelium-derived NOPlacental growth factorMyocardial hypertrophic responseDevelopment of hypertrophyDegradation of regulatorsMiR-182 targetsHemodynamic demandsPressure overloadPlGF expressionBlood supplyParacrine actionCardiomyocyte hypertrophyMyocardial angiogenesisCardiac angiogenesisTreatment inhibitsHypertrophyAKT/mTORC1 pathwaysNovel targetAkt/Growth factor
2014
The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury
Qi D, Atsina K, Qu L, Hu X, Wu X, Xu B, Piecychna M, Leng L, Fingerle-Rowson G, Zhang J, Bucala R, Young LH. The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury. Journal Of Clinical Investigation 2014, 124: 3540-3550. PMID: 24983315, PMCID: PMC4109524, DOI: 10.1172/jci73061.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorContractile dysfunctionAntibody-dependent neutralizationAutocrine/paracrine effectsCoronary artery ligationCardiac contractile dysfunctionMigration inhibitory factorLV contractile dysfunctionDopachrome tautomeraseMolecular signaling pathwaysArtery ligationIschemic injuryCardiac sizeCardiomyocyte secretionControl heartsProtective effectKnockout miceParacrine effectsIschemic stressPhysiologic responsesInhibitory factorMore necrosisDysfunctionInjuryMurine cardiomyocytes
2013
Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction
Wang J, Tong C, Yan X, Yeung E, Gandavadi S, Hare AA, Du X, Chen Y, Xiong H, Ma C, Leng L, Young LH, Jorgensen WL, Li J, Bucala R. Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction. Circulation 2013, 128: 225-236. PMID: 23753877, PMCID: PMC3781594, DOI: 10.1161/circulationaha.112.000862.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntigens, Differentiation, B-LymphocyteCardiotonic AgentsCells, CulturedGlucoseHistocompatibility Antigens Class IIIntramolecular OxidoreductasesIsoxazolesMacrophage Migration-Inhibitory FactorsMaleMiceMice, Inbred C57BLMice, KnockoutMyocardial InfarctionMyocardial IschemiaMyocytes, CardiacRecombinant ProteinsSignal TransductionConceptsMacrophage migration inhibitory factorCardiac ischemic injuryIschemic injuryProtective effectPostischemic left ventricular functionGlucose uptakeLeft coronary artery occlusionLeft ventricular functionCoronary artery occlusionIschemic tissue injuryMigration inhibitory factorMyocardial glucose uptakeAMPK activationTreatment of cardiomyocytesArtery occlusionMIF receptorVentricular functionIschemic myocardiumCellular glucose uptakeTissue injuryIschemia modelPharmacological augmentationFlow ischemiaSuch agonistsInhibitory factor
2009
Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion
Qi D, Hu X, Wu X, Merk M, Leng L, Bucala R, Young LH. Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion. Journal Of Clinical Investigation 2009, 119: 3807-3816. PMID: 19920350, PMCID: PMC2786800, DOI: 10.1172/jci39738.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineEnzyme ActivationHumansIn Vitro TechniquesIntramolecular OxidoreductasesJNK Mitogen-Activated Protein KinasesMacrophage Migration-Inhibitory FactorsMAP Kinase Kinase 4MiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMyocardial ContractionMyocardial Reperfusion InjuryMyocardiumReceptors, ImmunologicSignal TransductionConceptsMacrophage migration inhibitory factorIschemia/reperfusionMIF deficiencyCardiac injuryMIF allelesJNK pathway activationRole of MIFRecombinant macrophage migration inhibitory factorExperimental ischemia/reperfusionLow-expression MIF allelePathway activationGreater contractile dysfunctionMIF-/- miceMigration inhibitory factorJNK activationReperfusion injuryContractile dysfunctionCoronary occlusionProinflammatory cytokinesWT heartsReperfusionCell death (BAD) phosphorylationInjuryClinical implicationsInhibitory factor
2004
Cardiac myocyte‐specific HIF‐1α deletion alters vascularization, energy availability, calcium flux, and contractility in the normoxic heart
Huang Y, Hickey RP, Yeh JL, Liu D, Dadak A, Young LH, Johnson RS, Giordano FJ. Cardiac myocyte‐specific HIF‐1α deletion alters vascularization, energy availability, calcium flux, and contractility in the normoxic heart. The FASEB Journal 2004, 18: 1138-1140. PMID: 15132980, DOI: 10.1096/fj.04-1510fje.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium SignalingCoronary CirculationDNA-Binding ProteinsEnergy MetabolismGene DeletionGene Expression RegulationHeart Function TestsHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitMiceMice, Inbred C57BLMice, KnockoutMyocardial ContractionMyocardiumMyocytes, CardiacNeovascularization, PhysiologicNuclear ProteinsOxygen ConsumptionReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTranscription FactorsTranscription, GeneticConceptsCardiac functionCalcium fluxHypoxia-inducible transcription factor HIF-1alphaCardiac oxygen deliveryDisease statesHIF-1alphaSkeletal muscleCardiac contractile dysfunctionHigh-energy phosphate contentCardiovascular disease statesResting pulse rateTranscription factor HIF-1alphaCoronary vasodilatationMyocardial demandContractile dysfunctionMyocardial hibernationNormoxic heartsOxygen supplyGene expressionCalcium handlingOxygen deliveryPulse rateHeart muscleCardiac muscleMolecular pathology