2019
GDF15 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 temperatureInfectionMetabolismSepsisInflammationAdministrationHormoneAngiotensin 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
2012
AMP-Activated Protein Kinase Regulation and Biological Actions in the Heart
Zaha VG, Young LH. AMP-Activated Protein Kinase Regulation and Biological Actions in the Heart. Circulation Research 2012, 111: 800-814. PMID: 22935535, PMCID: PMC4397099, DOI: 10.1161/circresaha.111.255505.BooksConceptsAMPK pathwayProtein kinase regulationCellular fuel gaugeStress-activated kinasesRegulation of AMPKMaster metabolic regulatorNovel molecular mechanismBiological actionsKinase regulationDiverse biological actionsAMPK regulationProtein kinaseMolecular mechanismsMetabolic regulatorFuel gaugeImportant biological actionsRecent discoveryKinaseAMPKRegulationNew insightsPharmacological activationPathwayImportant roleTherapeutic potential
2011
A small molecule AMPK activator protects the heart against ischemia–reperfusion injury
Kim AS, Miller EJ, Wright TM, Li J, Qi D, Atsina K, Zaha V, Sakamoto K, Young LH. A small molecule AMPK activator protects the heart against ischemia–reperfusion injury. Journal Of Molecular And Cellular Cardiology 2011, 51: 24-32. PMID: 21402077, PMCID: PMC4005884, DOI: 10.1016/j.yjmcc.2011.03.003.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAMP-Activated Protein KinasesAnimalsApoptosisBiphenyl CompoundsCardiotonic AgentsEnzyme ActivatorsHeartIschemic PreconditioningMiceMice, Inbred C57BLMice, TransgenicMyocardial InfarctionMyocardial Reperfusion InjuryNecrosisNitric Oxide Synthase Type IIIPeptide Elongation Factor 2PyronesThiophenesConceptsIschemia-reperfusion injuryLeft ventricular contractile functionMyocardial ischemia-reperfusion injuryMouse heartsEndothelial nitric oxide synthase activationNitric oxide synthase activationLess myocardial necrosisCoronary artery occlusionIschemia-reperfusion damageVentricular contractile functionEukaryotic elongation factor 2Isolated mouse heartsPost-ischemic reperfusionAMPK activatorArtery occlusionIschemic contractureIschemic injuryInfarct sizeMyocardial stunningMyocardial necrosisCardioprotective mechanismsContractile functionSolid organsTherapeutic targetMyocardial apoptosis
2009
Diet-induced obesity obstructs insulin signaling in the heart
Young LH. Diet-induced obesity obstructs insulin signaling in the heart. AJP Heart And Circulatory Physiology 2009, 298: h306-h307. PMID: 19940075, DOI: 10.1152/ajpheart.01088.2009.Commentaries, Editorials and LettersAMP‐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
2004
Cardiac Abnormalities in Diabetic Patients With Neuropathy
Johnson BF, Nesto RW, Pfeifer MA, Slater WR, Vinik AI, Chyun DA, Law G, Wackers FJ, Young LH. Cardiac Abnormalities in Diabetic Patients With Neuropathy. Diabetes Care 2004, 27: 448-454. PMID: 14747227, DOI: 10.2337/diacare.27.2.448.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde ReductaseBenzothiazolesCardiac OutputDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2Diabetic NeuropathiesDouble-Blind MethodEnzyme InhibitorsExercise TestFemaleHeartHeart Conduction SystemHeart RateHumansMaleMiddle AgedPhthalazinesPlacebosStroke VolumeThiazolesVentricular Function, LeftConceptsLeft ventricular ejection fractionDiabetic patientsARI treatmentCardiac outputStroke volumeCardiac abnormalitiesAldose reductase inhibitorExercise left ventricular ejection fractionAbnormal heart rate variabilityDiastolic peak filling rateAsymptomatic cardiac abnormalitiesGated radionuclide ventriculographyMaximal bicycle exercisePlacebo-treated subjectsDiastolic filling rateVentricular ejection fractionCoronary artery diseaseValvular heart diseasePeak filling rateExercise cardiac outputLV stroke volumeHeart rate variabilityBlinded treatmentInsulin useArtery disease
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
2001
Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively treated type 1 diabetic patients
Russell R, Chyun D, Song S, Sherwin R, Tamborlane W, Lee F, Pfeifer M, Rife F, Wackers F, Young L. Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively treated type 1 diabetic patients. AJP Endocrinology And Metabolism 2001, 281: e1029-e1036. PMID: 11595660, DOI: 10.1152/ajpendo.2001.281.5.e1029.Peer-Reviewed Original ResearchMeSH KeywordsAdultCardiac OutputCatecholaminesChemical PrecipitationDiabetes Mellitus, Type 1DiastoleEpinephrineFatty Acids, NonesterifiedFemaleGlucagonGlucose Clamp TechniqueHeartHeart RateHumansHydrocortisoneHypoglycemiaInsulinLactic AcidMaleNorepinephrinePolyethylene GlycolsStroke VolumeSystoleVentricular Function, LeftConceptsType 1 diabetic patientsInsulin-induced hypoglycemiaNondiabetic groupType 1 diabetesDiabetic subjectsEuglycemic hyperinsulinemiaDiabetic patientsNondiabetic subjectsCardiac responseLeft ventricular systolicHealthy nondiabetic subjectsEquilibrium radionuclide angiographyDiabetic groupDiastolic functionVentricular systolicCardiovascular consequencesVentricular functionBlunted increaseCardiac outputGlucagon concentrationsPlasma catecholaminesRadionuclide angiographyInsulin infusionEuglycemic conditionsHypoglycemia
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
1995
Technetium-99m-nitroimidazole (BMS181321): a positive imaging agent for detecting myocardial ischemia.
Shi CQ, Sinusas AJ, Dione DP, Singer MJ, Young LH, Heller EN, Rinker BD, Wackers FJ, Zaret BL. Technetium-99m-nitroimidazole (BMS181321): a positive imaging agent for detecting myocardial ischemia. Journal Of Nuclear Medicine 1995, 36: 1078-86. PMID: 7769431.Peer-Reviewed Original ResearchConceptsIschemic regionMyocardial ischemiaBlood flowEx vivo SPECTRegional myocardial blood flowPartial coronary occlusionMicrosphere blood flowMyocardial blood flowOpen-chest canine modelVivo SPECT imagesSPECT imagesVivo planarCentral ischemic regionCoronary occlusionDemand ischemiaBMS181321Technetium-99mIntravenous injectionLiver ratioMyocardial imagingCanine modelPositive imagingHepatic clearanceLiver activityArterial sampling
1991
Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion.
Young LH, McNulty PH, Morgan C, Deckelbaum LI, Zaret BL, Barrett EJ. Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion. Journal Of Clinical Investigation 1991, 87: 554-560. PMID: 1991838, PMCID: PMC296343, DOI: 10.1172/jci115030.Peer-Reviewed Original ResearchConceptsBranched-chain amino acid infusionCoronary artery diseaseAmino acid infusionProtein turnoverBCAA infusionProtein synthesisArtery diseaseAcid infusionAmino acidsMyocardial protein turnoverCardiac double productCoronary blood flowPlasma insulin levelsMyocardial oxygen consumptionHuman heartProtein degradationNegative protein balanceEssential amino acidsMyocardial balanceInsulin levelsDouble productPhenylalanine balanceAnabolic effectsMyocardial uptakePostabsorptive patients
1988
Effect of Chronic Diabetes on Myocardial Fuel Metabolism and Insulin Sensitivity
Barrett E, Schwartz R, Young L, Jacob R, Zaret B. Effect of Chronic Diabetes on Myocardial Fuel Metabolism and Insulin Sensitivity. Diabetes 1988, 37: 943-948. PMID: 3290011, DOI: 10.2337/diab.37.7.943.Peer-Reviewed Original ResearchConceptsArterial free fatty acidsFree fatty acidsMyocardial balanceInsulin clampBranched-chain amino acid concentrationsEuglycemic insulin clamp techniqueGlucose uptakeInsulin-induced hypoaminoacidemiaInsulin clamp techniqueInsulin-deficient diabetesPlasma glucose concentrationFuel substrate metabolismSignificant myocardial uptakeEffect of insulinMyocardial fuel metabolismSignificant glucose uptakePhysiologic hyperinsulinemiaBasal periodChronic diabetesDiabetic animalsInsulin sensitivityAcute effectsAdditional dogsAmino acid concentrationsMyocardial uptake