2024
Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction
Rudokas M, McKay M, Toksoy Z, Eisen J, Bögner M, Young L, Akar F. Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction. Cardiovascular Diabetology 2024, 23: 261. PMID: 39026280, PMCID: PMC11264840, DOI: 10.1186/s12933-024-02357-1.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesMitochondrial network remodelingDamaged mitochondrial DNAEfficiency of oxidative phosphorylationImpaired ATP productionMitochondrial ultrastructural alterationsCardiac functionDiabetic heartCellular energy metabolismProduction of reactive oxygen speciesMitochondrial DNAMitochondrial networkMitochondrial fissionExcessive production of reactive oxygen speciesOxidative phosphorylationATP productionResponse to ischemic insultGlobal cardiac functionCell deathOverall cardiac functionCardiac ischemic injuryResponse to injuryCardiac mitochondriaIrreversible cell deathMitochondria
2022
Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation
Su KN, Ma Y, Cacheux M, Ilkan Z, Raad N, Muller GK, Wu X, Guerrera N, Thorn SL, Sinusas AJ, Foretz M, Viollet B, Akar JG, Akar FG, Young LH. Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation. JCI Insight 2022, 7: e141213. PMID: 35451373, PMCID: PMC9089788, DOI: 10.1172/jci.insight.141213.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAtrial FibrillationAtrial RemodelingConnexinsIon ChannelsMiceMyocytes, CardiacTranscription FactorsConceptsTranscription factorsKey transcription factorMaster metabolic regulatorIon channel subunitsGap junction proteinTranscriptional reprogrammingAMPK deletionProtein kinaseBiological functionsTranscriptional downregulationMetabolic regulatorChannel subunitsIon channelsAMPK expressionMetabolic stressAtrial fibrillationAMPKJunction proteinsElectrical excitabilityHomeostatic roleStructural remodelingConnexinsAtrial ion channelsRemodelingDownregulationMuscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy
Riaz M, Park J, Sewanan LR, Ren Y, Schwan J, Das SK, Pomianowski PT, Huang Y, Ellis MW, Luo J, Liu J, Song L, Chen IP, Qiu C, Yazawa M, Tellides G, Hwa J, Young LH, Yang L, Marboe CC, Jacoby DL, Campbell SG, Qyang Y. Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy. Circulation 2022, 145: 1238-1253. PMID: 35384713, PMCID: PMC9109819, DOI: 10.1161/circulationaha.121.056265.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathySarcomeric mutationsFamilial hypertrophic cardiomyopathySudden cardiac deathCardiac myosin heavy chainMechanism-based treatmentsDevelopment of hypertrophyActivated T cellsCalcineurin-nuclear factorForce productionPhenotypic expressionPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesHeart failureCardiac deathVentricular hypertrophyCell-derived cardiomyocytesCardiac contractilityPharmacological interventionsT cellsCardiac diseaseCardiac hypertrophyPatient-specific induced pluripotent stem cellsPharmacological meansTwitch relaxation
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 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
2015
AMPK and the Atrial Response to Metabolic Inhibition∗
Kim GE, Young LH. AMPK and the Atrial Response to Metabolic Inhibition∗. Journal Of The American College Of Cardiology 2015, 66: 59-61. PMID: 26139059, DOI: 10.1016/j.jacc.2015.04.054.Commentaries, Editorials and Letters
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 factorNO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth
Jaba IM, Zhuang ZW, Li N, Jiang Y, Martin KA, Sinusas AJ, Papademetris X, Simons M, Sessa WC, Young LH, Tirziu D. NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth. Journal Of Clinical Investigation 2013, 123: 1718-1731. PMID: 23454748, PMCID: PMC3613910, DOI: 10.1172/jci65112.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, BiologicalAnimalsCell EnlargementCells, CulturedCoronary VesselsEndothelium, VascularHeart VentriclesMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, TransgenicMultiprotein ComplexesMyocytes, CardiacNeovascularization, PhysiologicNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthasePlacenta Growth FactorPregnancy ProteinsProteinsProteolysisProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyRGS ProteinsSignal TransductionTOR Serine-Threonine KinasesConceptsCardiomyocyte growthAkt/mTORC1 signalingNovel NO-dependent mechanismProteasomal degradationCoordination of angiogenesisMTORC1 signalingConditional overexpressionMurine cardiac tissueG proteinsTransgenic expressionAkt/Physiological mechanismsMyocyte growthVessel growthGrowth factorTransgenic miceHypertrophic responseAngiogenesisKnockout miceMyocardial hypertrophyExpressionGrowthCardiac hypertrophyNOS inhibitor L-NAMEInduction
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