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
122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing Heart
GOEDEKE L, MA Y, ZHANG J, GUERRERA N, WU X, ZHANG D, KAHN M, ZHANG X, YOUNG L, SHULMAN G. 122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing Heart. Diabetes 2022, 71 DOI: 10.2337/db22-122-lb.Peer-Reviewed Original ResearchDAPA treatmentLV ejection fractionEjection fractionHeart failureMI ratsCardiac outputMyocardial infarctionCardiac functionLeft ventricularEffect of dapagliflozinMale Sprague-DawleyPlasma glucose concentrationMalonyl-CoA contentMitochondrial oxidationKetone availabilityΒOHB levelsVehicle treatmentPermanent ligationSGLT2 inhibitionSGLT2 inhibitorsCardioprotective effectsCoronary arteryAcetyl-CoA contentFailing HeartMitochondrial metabolism
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 mechanismGDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance
Luan HH, Wang A, Hilliard B, Carvalho F, Rosen CE, Ahasic A, Herzog E, Kang I, Pisani MA, Yu S, Zhang C, Ring A, Young L, Medzhitov R. GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance. Cell 2019, 178: 1231-1244.e11. PMID: 31402172, PMCID: PMC6863354, DOI: 10.1016/j.cell.2019.07.033.Peer-Reviewed Original ResearchConceptsViral infectionTriglyceride metabolismImpaired cardiac functionRole of GDF15Differentiation factor 15Plasma triglyceride levelsSympathetic outflowInflammatory damageTriglyceride levelsCardiac functionInflammatory responseExogenous administrationProtective effectFactor 15GDF15Central mediatorTissue toleranceBody temperatureInfectionMetabolismSepsisInflammationAdministrationHormone
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