2017
Up-regulation of Intracellular Calcium Handling Underlies the Recovery of Endotoxemic Cardiomyopathy in Mice
Morse JC, Huang J, Khona N, Miller EJ, Siwik DA, Colucci WS, Hobai IA. Up-regulation of Intracellular Calcium Handling Underlies the Recovery of Endotoxemic Cardiomyopathy in Mice. Anesthesiology 2017, 126: 1125-1138. PMID: 28410273, DOI: 10.1097/aln.0000000000001627.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCardiomyopathiesDisease Models, AnimalEndotoxemiaMaleMiceMice, Inbred C57BLMyocytes, CardiacSarcomeresUp-RegulationConceptsCalcium transientsCardiac recoveryLipopolysaccharide challengeCalcium handlingDay 3Sarcomere shorteningCardiomyocyte calcium handlingSepsis-induced cardiomyopathyVentricular ejection fractionIntracellular calcium handlingSarcoplasmic reticulum calcium loadMale C57BL/6 miceSodium/calcium exchangeMyocardial protein expressionSarcoplasmic reticulum calcium pumpSystemic inflammationEjection fractionEndotoxemic miceC57BL/6 miceMyocardial mechanismsCardiac functionCalcium loadCardiac contractilityBaseline levelsDay 6
2016
Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet‐Induced Metabolic Heart Disease
Sverdlov AL, Elezaby A, Qin F, Behring JB, Luptak I, Calamaras TD, Siwik DA, Miller EJ, Liesa M, Shirihai OS, Pimentel DR, Cohen RA, Bachschmid MM, Colucci WS. Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet‐Induced Metabolic Heart Disease. Journal Of The American Heart Association 2016, 5: e002555. PMID: 26755553, PMCID: PMC4859372, DOI: 10.1161/jaha.115.002555.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCatalaseDiet, High-FatDietary SucroseDisease Models, AnimalElectron Transport Complex IElectron Transport Complex IIEnergy MetabolismHypertrophy, Left VentricularMice, Inbred C57BLMice, TransgenicMitochondria, HeartMitochondrial DiseasesMutationOxidation-ReductionOxidative StressProtein Processing, Post-TranslationalReactive Oxygen SpeciesVentricular Dysfunction, LeftVentricular Function, LeftConceptsOxidative posttranslational modificationsMitochondrial reactive oxygen speciesPosttranslational modificationsReactive oxygen speciesMetabolic heart diseaseATP synthesisMitochondrial dysfunctionCardiac mitochondrial proteinsSite-directed mutationsMitochondrial proteinsTransgenic miceWild-type miceComplex IMitochondriaMitochondrial abnormalitiesHigh palmitateOxygen speciesCardiac mitochondriaCys100Mitochondrial consequencesCys103Key mediatorProteinH2O2 productionHigh-fat high-sucrose diet
2015
Partial Liver Kinase B1 (LKB1) Deficiency Promotes Diastolic Dysfunction, De Novo Systolic Dysfunction, Apoptosis, and Mitochondrial Dysfunction With Dietary Metabolic Challenge
Miller EJ, Calamaras T, Elezaby A, Sverdlov A, Qin F, Luptak I, Wang K, Sun X, Vijay A, Croteau D, Bachschmid M, Cohen RA, Walsh K, Colucci WS. Partial Liver Kinase B1 (LKB1) Deficiency Promotes Diastolic Dysfunction, De Novo Systolic Dysfunction, Apoptosis, and Mitochondrial Dysfunction With Dietary Metabolic Challenge. Journal Of The American Heart Association 2015, 5: e002277. PMID: 26722122, PMCID: PMC4859355, DOI: 10.1161/jaha.115.002277.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsApoptosisApoptosis Regulatory ProteinsCaspase 3DiastoleDiet, High-FatDietary SucroseDisease Models, AnimalGenetic Predisposition to DiseaseHeterozygoteHypertrophy, Left VentricularMice, KnockoutMitochondria, HeartMyocardiumPhenotypeProtein Serine-Threonine KinasesSignal TransductionSystoleTime FactorsTumor Suppressor Protein p53Tumor Suppressor ProteinsVentricular Dysfunction, LeftVentricular Function, LeftVentricular RemodelingConceptsHigh-sucrose dietSystolic dysfunctionDiastolic dysfunctionLiver kinase B1Metabolic heart diseaseDietary excessHeart diseaseMyocardial hypertrophyDe novo appearanceControl dietRestrictive filling patternSevere diastolic dysfunctionLeft ventricular dilationMitochondrial dysfunctionMetabolic stressWild-type miceHigh-sucrose feedingNovo appearanceP53/PUMAMore hypertrophyDiastolic functionMyocardial dysfunctionVentricular hypertrophyVentricular dilationSevere mitochondrial dysfunctionAMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism
Sung MM, Zordoky BN, Bujak AL, Lally JS, Fung D, Young ME, Horman S, Miller EJ, Light PE, Kemp BE, Steinberg GR, Dyck JR. AMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism. Cardiovascular Research 2015, 107: 235-245. PMID: 26023060, PMCID: PMC4565988, DOI: 10.1093/cvr/cvv166.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsCardiomegalyCardiomyopathy, DilatedDisease Models, AnimalEnergy MetabolismMice, KnockoutMyocardial ContractionConceptsHeart failureCardiac functionCardiac hypertrophyRole of AMPKAMPK deficiencyCompensatory cardiac hypertrophyWild-type littermatesFatty acid oxidation ratesMyocardial energy metabolismAlters cardiac functionMuscle-specific deletionFirst mouse modelDiastolic functionAbsence of changesCardiac dysfunctionWT miceBasal glucoseMyocardial functionMyocardial metabolismCell shorteningMouse modelCardiac muscle resultsHypertrophyImpaired activationTroponin I