2019
Cardiomyocyte 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 VEGFAngiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure
Pfau D, Thorn SL, Zhang J, Mikush N, Renaud JM, Klein R, deKemp RA, Wu X, Hu X, Sinusas AJ, Young LH, Tirziu D. Angiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure. Scientific Reports 2019, 9: 5791. PMID: 30962467, PMCID: PMC6453892, DOI: 10.1038/s41598-019-42113-0.Peer-Reviewed Original ResearchMeSH KeywordsAminobutyratesAngiotensin Receptor AntagonistsAnimalsBiphenyl CompoundsDrug CombinationsHeartHeart FailureMaleMyocardial Reperfusion InjuryMyocardiumNeovascularization, PhysiologicNeprilysinOrganotechnetium CompoundsPeptides, CyclicRatsRats, Inbred LewSingle Photon Emission Computed Tomography Computed TomographyTetrazolesValsartanVascular Endothelial Growth Factor AVentricular RemodelingConceptsSacubitril/valsartanExperimental heart failureHeart failureMyocardial infarctionMyocardial remodelingAngiotensin receptor neprilysin inhibitorAngiotensin receptor blocker valsartanMicroSPECT/CT imagingReceptor blocker valsartanHeart failure patientsProgressive LV dilationGlobal LV functionLV contractile dysfunctionNeprilysin inhibitor sacubitrilBorder zoneLimited remodelingFailure patientsInhibitor therapyMale LewisWeeks treatmentLV dilationLV functionNeprilysin inhibitorContractile dysfunctionInterstitial fibrosis
2015
AMPK: energy sensor and survival mechanism in the ischemic heart
Qi D, Young LH. AMPK: energy sensor and survival mechanism in the ischemic heart. Trends In Endocrinology And Metabolism 2015, 26: 422-429. PMID: 26160707, PMCID: PMC4697457, DOI: 10.1016/j.tem.2015.05.010.BooksConceptsIschemic heartAMPK activationEndoplasmic reticulum stressFatty acid metabolismCardioprotective strategiesContractile dysfunctionMyocardial infarctionMyocardial ischemiaPotential therapeutic applicationsVascular diseaseMyocardial necrosisPharmacological activationReticulum stressAcid metabolismProtein kinaseIschemiaMitochondrial functionEnergy sensorCellular metabolismSurvival mechanismCritical regulatorActivationHeartNovel mechanismTherapeutic applications
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
Urocortin 2 autocrine/paracrine and pharmacologic effects to activate AMP-activated protein kinase in the heart
Li J, Qi D, Cheng H, Hu X, Miller EJ, Wu X, Russell KS, Mikush N, Zhang J, Xiao L, Sherwin RS, Young LH. Urocortin 2 autocrine/paracrine and pharmacologic effects to activate AMP-activated protein kinase in the heart. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 16133-16138. PMID: 24043794, PMCID: PMC3791748, DOI: 10.1073/pnas.1312775110.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl-CoA CarboxylaseAMP-Activated Protein KinasesAnalysis of VarianceAnimalsAntibodies, NeutralizingCorticotropin-Releasing HormoneEnzyme ActivationImmunoblottingImmunohistochemistryMiceMyocardiumPeptide FragmentsPhosphorylationReceptors, Corticotropin-Releasing HormoneReperfusion InjurySignal TransductionUrocortinsConceptsIschemia/reperfusionIschemia/reperfusion injuryUCN2 treatmentReperfusion injuryContractile dysfunctionRegional ischemia/reperfusionAMPK activationHeart muscleIschemic AMPK activationAutocrine/paracrine pathwayCardiac contractile dysfunctionAutocrine/paracrine factorCorticotropin-releasing factor (CRF) familyIsolated heart muscleCRFR2 antagonistAcetyl-CoA carboxylase phosphorylationCardiac damageMyocardial injuryCRF receptorsPharmacologic effectsUrocortin 2ΕV1-2Activation of AMPParacrine pathwaysReperfusion
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
2005
AMP-Activated Protein Kinase: A Key Stress Signaling Pathway in the Heart
Young LH, Li J, Baron SJ, Russell RR. AMP-Activated Protein Kinase: A Key Stress Signaling Pathway in the Heart. Trends In Cardiovascular Medicine 2005, 15: 110-118. PMID: 16039971, DOI: 10.1016/j.tcm.2005.04.005.BooksConceptsLeft ventricular contractile dysfunctionVentricular contractile dysfunctionFatty acid oxidationProtein kinaseCardiovascular actionsHeart failureContractile dysfunctionWolff-ParkinsonWhite syndromeTransgenic miceGlycogen overloadStress Signaling PathwaysImportant regulatory mechanismSignaling pathwaysHeartAcid oxidationGlucose transportMolecular mechanismsAnabolic pathwaysRegulatory mechanismsAMP
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