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
2017
MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics
Tilstam PV, Qi D, Leng L, Young L, Bucala R. MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics. Expert Opinion On Therapeutic Targets 2017, 21: 671-683. PMID: 28562118, PMCID: PMC6130320, DOI: 10.1080/14728222.2017.1336227.BooksConceptsMacrophage migration inhibitory factorMIF family membersCardiovascular diseaseFamily cytokinesTherapeutic opportunitiesIschemia-reperfusion injuryChemokine-like functionsMigration inhibitory factorNovel therapeutic opportunitiesPro-survival mediatorsFamily membersInflammatory pathogenesisMyocardial infarctionMyocardial ischemiaClinical studiesPleiotropic cytokineImmune systemInhibitory factorReceptor pathwayCytokinesDiseaseMIF-2Active investigationMIF familyClinical translation
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.BooksMeSH KeywordsAMP-Activated Protein KinasesAnimalsHumansMyocardial IschemiaMyocardial Reperfusion InjuryConceptsIschemic 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
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
AMP‐activated protein kinase: a core signalling pathway in the heart
Kim AS, Miller EJ, Young LH. AMP‐activated protein kinase: a core signalling pathway in the heart. Acta Physiologica 2009, 196: 37-53. PMID: 19239414, DOI: 10.1111/j.1748-1716.2009.01978.x.BooksConceptsProtein kinaseEssential cellular processesTumor suppressor LKB1Downstream AMPK targetsProduction of ATPProtein phosphataseAMPK targetsActivated AMPKIntracellular glycogen accumulationCellular processesUpstream kinaseFatty acid metabolismCardiac myocyte hypertrophyAMPK activationAMPK activityImportant intracellularMolecular mechanismsMajor regulatorAMPKProtein synthesisKinaseAcid metabolismOral hypoglycaemic drugsGlycogen accumulationType 2 diabetes
2008
AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra
Young LH. AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra. Circulation 2008, 117: 832-840. PMID: 18268160, DOI: 10.1161/circulationaha.107.713115.BooksMacrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart
Miller EJ, Li J, Leng L, McDonald C, Atsumi T, Bucala R, Young LH. Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature 2008, 451: 578-582. PMID: 18235500, DOI: 10.1038/nature06504.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntigens, Differentiation, B-LymphocyteCoronary Artery DiseaseEnzyme ActivationGenetic Predisposition to DiseaseGenotypeGlucoseHistocompatibility Antigens Class IIHumansHypoxiaMacrophage Migration-Inhibitory FactorsMiceMultienzyme ComplexesMyocardial IschemiaMyocardial Reperfusion InjuryMyocardiumPolymorphism, GeneticPromoter Regions, GeneticProtein Serine-Threonine KinasesRatsSignal TransductionConceptsIschemic heartMacrophage migration inhibitory factorLower MIF levelsCoronary artery diseaseIschemic heart diseaseMigration inhibitory factorPotential risk markerMIF levelsArtery diseaseRisk markersHeart diseaseIschemic stressCytokine MIFInhibitory factorGlucose uptakePotential drug targetsDiseaseHeartDrug targetsCellular stress responseAMPKMaster regulatorNew studiesPatientsAtherosclerosis
2007
Resolution of Asymptomatic Myocardial Ischemia in Patients With Type 2 Diabetes in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) Study
Wackers FJ, Chyun DA, Young LH, Heller GV, Iskandrian AE, Davey JA, Barrett EJ, Taillefer R, Wittlin SD, Filipchuk N, Ratner RE, Inzucchi SE. Resolution of Asymptomatic Myocardial Ischemia in Patients With Type 2 Diabetes in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) Study. Diabetes Care 2007, 30: 2892-2898. PMID: 17682123, DOI: 10.2337/dc07-1250.Peer-Reviewed Original ResearchConceptsResolution of ischemiaType 2 diabetesDetection of ischemiaNew ischemiaAsymptomatic Diabetics (DIAD) studyCardiovascular risk factorsAsymptomatic myocardial ischemiaAdenosine stress myocardial perfusionRepeat stressIschemia increasesAsymptomatic patientsCardiac eventsMore patientsACE inhibitorsMyocardial ischemiaRisk factorsIntensive treatmentDiabetic studyIschemiaMyocardial perfusionPatientsMedical treatmentDiabetesInitial evaluationGreater increase
2006
Value of peripheral vascular endothelial function in the detection of relative myocardial ischemia in asymptomatic type 2 diabetic patients who underwent myocardial perfusion imaging
Papaioannou GI, Kasapis C, Seip RL, Grey NJ, Katten D, Wackers FJ, Inzucchi SE, Engel S, Taylor A, Young LH, Chyun DA, Davey JA, Iskandrian AE, Ratner RE, Robinson EC, Carolan S, Heller GV. Value of peripheral vascular endothelial function in the detection of relative myocardial ischemia in asymptomatic type 2 diabetic patients who underwent myocardial perfusion imaging. Journal Of Nuclear Cardiology 2006, 13: 362-368. PMID: 16750781, DOI: 10.1016/j.nuclcard.2006.01.022.Peer-Reviewed Original ResearchConceptsEndothelium-dependent vasodilationEndothelium-independent vasodilationCoronary artery diseaseMyocardial perfusion imagingRelative myocardial ischemiaAsymptomatic patientsEndothelial functionNegative predictive valueMyocardial ischemiaAsymptomatic type 2 diabetic patientsExclusion of CADPredictive valueAdenosine myocardial perfusion imagingPeripheral vascular endothelial functionType 2 diabetic patientsType 2 diabetes mellitusHigh negative predictive valueAsymptomatic Diabetics (DIAD) studyBrachial artery ultrasonographyVascular endothelial functionDetection of ischemiaEDV responseRelative ischemiaEndothelial dysfunctionOvert atherosclerosisActivation of AMPK α- and γ-isoform complexes in the intact ischemic rat heart
Li J, Coven DL, Miller EJ, Hu X, Young ME, Carling D, Sinusas AJ, Young LH. Activation of AMPK α- and γ-isoform complexes in the intact ischemic rat heart. AJP Heart And Circulatory Physiology 2006, 291: h1927-h1934. PMID: 16648175, DOI: 10.1152/ajpheart.00251.2006.Peer-Reviewed Original ResearchConceptsAMPK activityAMPK complexAlpha subunit activationDifferent subunit isoformsSerine-threonine kinaseCellular metabolic processesGamma subunit isoformsRegulatory betaAlpha-subunit contentHeterotrimeric complexProtein kinaseAMPK αMultiple isoformsKinase activitySubunit isoformsMetabolic processesAMPK phosphorylationAMPKIsoformsPhysiological regulationKinaseMutationsComplexesKey rolePathophysiological importance
2005
AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart
Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR, Young LH. AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart. Circulation Research 2005, 97: 872-879. PMID: 16179588, DOI: 10.1161/01.res.0000187458.77026.10.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsAnisomycinCell HypoxiaEnzyme ActivationGlucoseGlucose Transporter Type 4Intracellular Signaling Peptides and ProteinsMaleMAP Kinase Kinase 3MiceMice, Inbred C57BLMice, TransgenicMultienzyme ComplexesMyocardial IschemiaP38 Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesProtein TransportRatsRats, Sprague-DawleyRibonucleotidesConceptsMitogen-activated protein kinaseP38 mitogen-activated protein kinaseMAPK kinase 3P38 MAPK activationAlpha2 catalytic subunitProtein kinaseMAPK activationCatalytic subunitGlucose transportStress-signaling pathwaysAMPK activator 5Role of AMPKProtein kinase 1Direct molecular targetP38 MAPK inhibitorMouse heartsAMPK complexProtein TAB1Scaffold proteinGLUT4 translocationUpstream kinaseAMPK activationKinase 3Kinase 1MAPK inhibitorDual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart
Baron SJ, Li J, Russell RR, Neumann D, Miller EJ, Tuerk R, Wallimann T, Hurley RL, Witters LA, Young LH. Dual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart. Circulation Research 2005, 96: 337-345. PMID: 15653571, DOI: 10.1161/01.res.0000155723.53868.d2.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine MonophosphateAdenosine TriphosphateAminoimidazole CarboxamideAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsInfusions, IntravenousMaleMultienzyme ComplexesMyocardial IschemiaMyocardiumPhosphorylationProtein KinasesProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyRecombinant ProteinsRibonucleotidesConceptsRecombinant AMPKAMPKK activityAMPK phosphorylationPhosphorylation of Thr172Gamma regulatory subunitsIschemic heartImportant signaling proteinAlpha catalytic subunitRat heartHeterotrimeric AMPKAMPKKHeterotrimeric complexActivation loopRegulatory subunitKinase actionSignaling proteinsCatalytic subunitProtein kinaseAMPK activityLow-flow ischemiaGamma subunitsAMPKInteraction of AMPPhosphorylationAddition of AMP
2004
AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury
Russell RR, Li J, Coven DL, Pypaert M, Zechner C, Palmeri M, Giordano FJ, Mu J, Birnbaum MJ, Young LH. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. Journal Of Clinical Investigation 2004, 114: 495-503. PMID: 15314686, PMCID: PMC503766, DOI: 10.1172/jci19297.Peer-Reviewed Original ResearchConceptsLow-flow ischemiaGlucose uptakePostischemic reperfusionWT heartsLeft ventricular dPNormal fractional shorteningLV contractile functionPostischemic cardiac dysfunctionInsulin-stimulated glucose uptakeImportant protective roleLong-term inhibitionFatty acid oxidationFractional shorteningHeart failureVentricular dPCardiac consequencesCardiac dysfunctionCaspase-3 activityMyocardial ischemiaContractile functionReperfusionCardiac hypertrophyIschemiaTransgenic miceProtective roleDetection of Silent Myocardial Ischemia in Asymptomatic Diabetic Subjects
Wackers FJ, Young LH, Inzucchi SE, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Wittlin SD, Heller GV, Filipchuk N, Engel S, Ratner RE, Iskandrian AE. Detection of Silent Myocardial Ischemia in Asymptomatic Diabetic Subjects. Diabetes Care 2004, 27: 1954-1961. PMID: 15277423, DOI: 10.2337/diacare.27.8.1954.Peer-Reviewed Original ResearchConceptsSilent myocardial ischemiaType 2 diabetesCardiac risk factorsMyocardial ischemiaAsymptomatic patientsSilent ischemiaNormal perfusionRisk factorsTraditional cardiac risk factorsAmerican Diabetes Association guidelinesTomography myocardial perfusion imagingRegional myocardial perfusion abnormalitiesAbnormal stress testAsymptomatic diabetic subjectsAsymptomatic Diabetics (DIAD) studyCurrent American Diabetes AssociationPrevalence of ischemiaCardiac autonomic dysfunctionLarge perfusion defectsST-segment depressionCoronary artery diseaseAmerican Diabetes AssociationMyocardial perfusion abnormalitiesMyocardial perfusion imagingStrongest predictor
2003
Diagnosis of CAD in patients with diabetes: Who to evaluate
Young LH, Jose P, Chyun D. Diagnosis of CAD in patients with diabetes: Who to evaluate. Current Diabetes Reports 2003, 3: 19-27. PMID: 12643142, DOI: 10.1007/s11892-003-0048-3.BooksMeSH KeywordsCoronary DiseaseDiabetes ComplicationsHeart Function TestsHumansMass ScreeningMyocardial IschemiaPrognosisRisk FactorsConceptsCoronary artery diseaseCardiac testingDiabetic patientsDiagnosis of CADNoninvasive cardiac testingManagement of patientsCAD screeningAsymptomatic ischemiaAsymptomatic patientsSymptomatic patientsArtery diseaseCardiac catheterizationRisk stratificationPatientsAccurate diagnosisDiagnosisAppropriate useDiabetesEffective diagnosisCurrent controversiesRecent informationRevascularizationCatheterizationIschemiaClinicians
2002
Correlation of myocardial p-(123)I-iodophenylpentadecanoic acid retention with (18)F-FDG accumulation during experimental low-flow ischemia.
Shi CQ, Young LH, Daher E, DiBella EV, Liu YH, Heller EN, Zoghbi S, Wackers FJ, Soufer R, Sinusas AJ. Correlation of myocardial p-(123)I-iodophenylpentadecanoic acid retention with (18)F-FDG accumulation during experimental low-flow ischemia. Journal Of Nuclear Medicine 2002, 43: 421-31. PMID: 11884504.Peer-Reviewed Original Research
2000
Cellular and molecular regulation of cardiac glucose transport
Young L, Coven D, Russell R. Cellular and molecular regulation of cardiac glucose transport. Journal Of Nuclear Cardiology 2000, 7: 267-276. PMID: 10888399, DOI: 10.1016/s1071-3581(00)70016-x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
1999
Regulation of myocardial glucose uptake and transport during ischemia and energetic stress
Young L, Russell R, Yin R, Caplan M, Ren J, Bergeron R, Shulman G, Sinusas A. Regulation of myocardial glucose uptake and transport during ischemia and energetic stress. The American Journal Of Cardiology 1999, 83: 25-30. PMID: 10750583, DOI: 10.1016/s0002-9149(99)00253-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEnergetic stressEnergy-generating metabolic pathwaysMonophosphate-activated protein kinaseGlucose uptakeGlucose transport proteinProtein kinaseTransporter translocationTransport proteinsMolecular mechanismsMetabolic pathwaysCardiac glucose uptakeGlucose transporterCellular mechanismsGlucose transportFuel gaugeKinaseTranslocationGlucose entryModerate regional ischemiaSubsequent metabolismGlucose utilization increasesImportant roleUptakeGLUT4Stress
1998
Additive Effects of Hyperinsulinemia and Ischemia on Myocardial GLUT1 and GLUT4 Translocation In Vivo
Russell R, Yin R, Caplan M, Hu X, Ren J, Shulman G, Sinusas A, Young L. Additive Effects of Hyperinsulinemia and Ischemia on Myocardial GLUT1 and GLUT4 Translocation In Vivo. Circulation 1998, 98: 2180-2186. PMID: 9815873, DOI: 10.1161/01.cir.98.20.2180.Peer-Reviewed Original Research
1997
Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo.
Young L, Renfu Y, Russell R, Hu X, Caplan M, Ren J, Shulman G, Sinusas A. Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo. Circulation 1997, 95: 415-22. PMID: 9008459, DOI: 10.1161/01.cir.95.2.415.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportDogsFluorescent Antibody TechniqueGlucose Transporter Type 1Glucose Transporter Type 4HeartIntracellular MembranesMonosaccharide Transport ProteinsMuscle ProteinsMyocardial IschemiaMyocardiumRegional Blood FlowSarcolemmaSubcellular FractionsTissue Distribution