2024
De Novo Elastin Assembly Alleviates Development of Supravalvular Aortic Stenosis—Brief Report
Ellis M, Riaz M, Huang Y, Anderson C, Hoareau M, Li X, Luo H, Lee S, Park J, Luo J, Batty L, Huang Q, Lopez C, Reinhardt D, Tellides G, Qyang Y. De Novo Elastin Assembly Alleviates Development of Supravalvular Aortic Stenosis—Brief Report. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: 1674-1682. PMID: 38752350, PMCID: PMC11209776, DOI: 10.1161/atvbaha.124.320790.Peer-Reviewed Original ResearchSupravalvular aortic stenosisVascular smooth muscle cellsSmooth muscle cellsMuscle cellsAortic stenosisMedial vascular smooth muscle cellsVascular proliferative diseasesEpigallocatechin gallate treatmentProliferative abnormalitiesPreclinical findingsHeart failureLuminal occlusionMouse modelCell hyperproliferationDefective elastinProliferative diseasesCardiovascular disordersFormation of elastinTherapeutic interventionsElastin assemblyElastin depositionStenosisMiceAortic mechanicsImproper formation
2019
Tissue-Engineered Stem Cell Models of Cardiovascular Diseases
Anderson C, Luo J, Sewanan L, Kural M, Riaz M, Park J, Huang Y, Niklason L, Campbell S, Qyang Y. Tissue-Engineered Stem Cell Models of Cardiovascular Diseases. 2019, 1-18. DOI: 10.1007/978-3-030-20047-3_1.ChaptersMolecular underpinningsStem cell modelTwo-dimensional cell culture methodsComplex 3D microenvironmentThree-dimensional microenvironmentMolecular mechanismsTissue-engineered modelDisease modelingNew therapeutic strategiesCell culturesCell culture methodsCell modelPathological conditionsCulture systemDisease statesCompelling insightsTherapeutic strategiesMicroenvironmentCulture methodVivoUse of Human Cells and Heart Muscle Tissue Patches as Therapeutics for Heart Diseases
Batty L, Ellis M, Anderson C, Luo J, Riaz M, Park J, Das S, Huang Y, Jacoby D, Campbell S, Qyang Y. Use of Human Cells and Heart Muscle Tissue Patches as Therapeutics for Heart Diseases. 2019 DOI: 10.1016/b978-0-12-801238-3.65542-3.ChaptersCardiac tissue engineeringThree-dimensional tissuesCardiovascular disease epidemicRegenerative medicineTissue engineeringCardiac patchesCardiovascular healthHeart diseaseInfarcted tissueClinical useHydrogel matrixStem cellsCardiomyocytesTissue patchesRecent innovationsDisease epidemicsTissueFurther researchHuman cells
2016
Endothelial Nogo-B regulates sphingolipid biosynthesis to promote the transition from hypertrophy to heart failure during chronic pressure overload
Zhang Y, Huang Y, Cantalupo A, Azevedo P, Siragusa M, Giordano F, Di Lorenzo A. Endothelial Nogo-B regulates sphingolipid biosynthesis to promote the transition from hypertrophy to heart failure during chronic pressure overload. International Journal Of Cardiology Cardiovascular Risk And Prevention 2016, 10: e2. DOI: 10.1016/j.jash.2016.03.006.Peer-Reviewed Original Research
2013
Activation of Hypoxia‐Inducible Factor‐2 in Adipocytes Results in Pathological Cardiac Hypertrophy
Lin Q, Huang Y, Booth CJ, Haase VH, Johnson RS, Simon M, Giordano FJ, Yun Z. Activation of Hypoxia‐Inducible Factor‐2 in Adipocytes Results in Pathological Cardiac Hypertrophy. Journal Of The American Heart Association 2013, 2: e000548. PMID: 24326162, PMCID: PMC3886757, DOI: 10.1161/jaha.113.000548.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsBasic Helix-Loop-Helix Transcription FactorsCardiomegalyCytokinesDisease Models, AnimalGene Expression RegulationGenetic Predisposition to DiseaseHypoxia-Inducible Factor 1, alpha SubunitInflammation MediatorsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMyocytes, CardiacPhenotypeSignal TransductionTime FactorsVon Hippel-Lindau Tumor Suppressor ProteinConceptsPathological cardiac hypertrophyCardiac hypertrophyHypoxia-inducible factor-2Hypoxia-signaling pathwayHypoxia-inducible factor (HIF) pathwayVon Hippel-Lindau (VHL) geneTranscription factorsUncharacterized mechanismAdipose tissueAdipocytes resultsHIF activationObesity-associated cardiomyopathyChemotactic protein-1Protein 1Activated T cellsDirect roleEssential roleCardiomyopathy-associated genesFactor 2Genetic deletionFactor pathwayUndefined mechanismDeletionNuclear factorGenes
2012
IL-13 receptor α2-arginase 2 pathway mediates IL-13-induced pulmonary hypertension
Cho WK, Lee CM, Kang MJ, Huang Y, Giordano FJ, Lee PJ, Trow TK, Homer RJ, Sessa WC, Elias JA, Lee CG. IL-13 receptor α2-arginase 2 pathway mediates IL-13-induced pulmonary hypertension. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2012, 304: l112-l124. PMID: 23125252, PMCID: PMC3543640, DOI: 10.1152/ajplung.00101.2012.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionIL-13Human pulmonary artery smooth muscle cellsDevelopment of PHPulmonary artery smooth muscle cellsRight ventricle systolic pressurePathogenesis of PHArtery smooth muscle cellsExpression of ARG2Pulmonary arterial hypertensionPulmonary vascular remodelingVentricle systolic pressurePotential therapeutic targetIL-13 treatmentSmooth muscle cellsNull mutant miceArterial hypertensionEffector cytokinesMedial thickeningSystolic pressureHemodynamic changesPulmonary arterySmall-interfering RNAVascular remodelingArginase-2Engineered Zinc-Finger Proteins Can Compensate Genetic Haploinsufficiency by Transcriptional Activation of the Wild-Type Allele: Application to Willams-Beuren Syndrome and Supravalvular Aortic Stenosis
Zhang P, Huang A, Morales-Ruiz M, Starcher BC, Huang Y, Sessa WC, Niklason LE, Giordano FJ. Engineered Zinc-Finger Proteins Can Compensate Genetic Haploinsufficiency by Transcriptional Activation of the Wild-Type Allele: Application to Willams-Beuren Syndrome and Supravalvular Aortic Stenosis. Human Gene Therapy 2012, 23: 1186-1199. PMID: 22891920, PMCID: PMC3498887, DOI: 10.1089/hum.2011.201.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAortic Stenosis, SupravalvularCell LineCell MovementCell ProliferationDosage Compensation, GeneticElastinGene ExpressionGene Expression RegulationHaploinsufficiencyHumansMutationNonsense Mediated mRNA DecayOrgan SpecificityProtein EngineeringTranscriptional ActivationWilliams SyndromeZinc FingersConceptsZinc finger protein transcription factorsTranscriptional activationWild-type alleleWilliams-Beuren syndromeMutant allelesEngineered Zinc Finger ProteinsElastin geneTargeted transcriptional activationCompensatory expressionSplice variantsZinc finger proteinProtein transcription factorsNonsense-mediated decayWild-type cellsMultiple splice variantsElastin expressionGene replacement strategyMutant proteinsHaploinsufficient genesTranscription factorsComplex genesNatural stoichiometryDistinct genetic syndromesGenesGenetic diseasesA Designed Zinc-finger Transcriptional Repressor of Phospholamban Improves Function of the Failing Heart
Zhang HS, Liu D, Huang Y, Schmidt S, Hickey R, Guschin D, Su H, Jovin IS, Kunis M, Hinkley S, Liang Y, Hinh L, Spratt SK, Case CC, Rebar EJ, Ehrlich BE, Ehrlich B, Gregory P, Giordano F. A Designed Zinc-finger Transcriptional Repressor of Phospholamban Improves Function of the Failing Heart. Molecular Therapy 2012, 20: 1508-1515. PMID: 22828502, PMCID: PMC3412484, DOI: 10.1038/mt.2012.80.Peer-Reviewed Original ResearchConceptsHeart failureZinc finger protein transcription factorsSingle gene regulationZinc finger transcriptional repressorDiverse DNA sequencesProtein transcription factorsDisease-related genesDisease-related proteinsGene repressionZFP TFsTranscriptional repressorTranscription factorsDNA sequencesPotent repressionPLN expressionHuman diseasesRepressorContractile functionDrug targetsFailing HeartTherapeutic inhibitionAnimal modelsReuptake kineticsRepressionTherapeutic interventionsmiR-1 mediated suppression of Sorcin regulates myocardial contractility through modulation of Ca2+ signaling
Ali R, Huang Y, Maher SE, Kim RW, Giordano FJ, Tellides G, Geirsson A. miR-1 mediated suppression of Sorcin regulates myocardial contractility through modulation of Ca2+ signaling. Journal Of Molecular And Cellular Cardiology 2012, 52: 1027-1037. PMID: 22326846, DOI: 10.1016/j.yjmcc.2012.01.020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCalcium SignalingCalcium-Binding ProteinsCardiac VolumeCardiomyopathiesCell LineDEAD-box RNA HelicasesHeartHumansMaleMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutMicroRNAsMyocardial ContractionMyocardiumRibonuclease IIIRNA InterferenceRNA, Small InterferingUp-RegulationConceptsCardiac functionMiR-1Normal cardiac contractile functionEnd-stage cardiomyopathyCardiac contractile functionWild-type miceCalcium signalingExcitation-contraction couplingModulation of Ca2Cultured mouse cardiomyocytesAcute cardiomyopathyMiR-1 targetsHeart failureMyocardial contractilityMiR-1 knockdownContractile functionAntagomir treatmentSorcin expressionCalcium homeostasisKnockdown miceSorcin levelsCardiac phenotypeMouse cardiomyocytesCritical mediatorPathological relevance
2010
Cellular Endocytosis and Gene Delivery
Ziello J, Huang Y, Jovin I. Cellular Endocytosis and Gene Delivery. Molecular Medicine 2010, 16: 222-229. PMID: 20454523, PMCID: PMC2864810, DOI: 10.2119/molmed.2009.00101.Peer-Reviewed Original ResearchConceptsGene therapyNonviral vectorsClathrin-independent endocytic processVariety of vectorsUnderstanding of endocytosisClathrin-dependent endocytosisCurrent molecular medicineMechanism of endocytosisGene deliveryLipid raftsEndocytic processVector deliveryCellular traffickingCellular endocytosisEndocytosisMolecular medicineTraffickingTarget cellsCellsMetabolic diseasesTherapeutic potentialCaveolaeGenesDeliveryAdeno
2008
Hypoxia-Inducible Factor-Dependent Degeneration, Failure, and Malignant Transformation of the Heart in the Absence of the von Hippel-Lindau Protein
Lei L, Mason S, Liu D, Huang Y, Marks C, Hickey R, Jovin IS, Pypaert M, Johnson RS, Giordano FJ. Hypoxia-Inducible Factor-Dependent Degeneration, Failure, and Malignant Transformation of the Heart in the Absence of the von Hippel-Lindau Protein. Molecular And Cellular Biology 2008, 28: 3790-3803. PMID: 18285456, PMCID: PMC2423296, DOI: 10.1128/mcb.01580-07.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCapillariesCell Transformation, NeoplasticErbB ReceptorsGene DeletionGene Transfer TechniquesHeart FailureHeart NeoplasmsHypoxiaHypoxia-Inducible Factor 1, alpha SubunitLipid MetabolismLipidsMiceMice, KnockoutMyocardiumNeovascularization, PhysiologicPhosphorylationProto-Oncogene Proteins c-metRas ProteinsVon Hippel-Lindau Tumor Suppressor ProteinConceptsHeart failureVon Hippel-Lindau proteinChronic activationAdvanced ischemic heart diseaseMalignant cardiac tumorsHIF-1alphaProgressive heart failureIschemic heart diseaseCardiac myocyte-specific deletionHIF pathwayHuman heart failureFeatures of rhabdomyosarcomaHypoxia-inducible factorHypoxia-inducible transcription factor-1Cardiac tumorsHeart diseaseTranscription factor 1Cardiac degenerationIschemic heartMyocyte lossDependent degenerationMalignant transformationPremature deathLipid accumulationCardiac muscleChromogranin B Regulates Calcium Signaling, Nuclear Factor &kgr;B Activity, and Brain Natriuretic Peptide Production in Cardiomyocytes
Heidrich FM, Zhang K, Estrada M, Huang Y, Giordano FJ, Ehrlich BE. Chromogranin B Regulates Calcium Signaling, Nuclear Factor &kgr;B Activity, and Brain Natriuretic Peptide Production in Cardiomyocytes. Circulation Research 2008, 102: 1230-1238. PMID: 18420944, PMCID: PMC2952358, DOI: 10.1161/circresaha.107.166033.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAngiotensin IIAnimalsCalciumCalcium SignalingCardiomegalyCells, CulturedChromogranin BInositol 1,4,5-Trisphosphate ReceptorsMyocytes, CardiacNatriuretic Peptide, BrainNFATC Transcription FactorsNF-kappa BPromoter Regions, GeneticRatsTranscription, GeneticVasoconstrictor AgentsConceptsBrain natriuretic peptideAngiotensin IICardiac hypertrophyBNP productionChromogranin BNuclear factorNuclear factor-kappaB activityNatriuretic peptide productionActivated T cellsNuclear factor-kappaBLuciferase reporter assaysHeart failureNatriuretic peptideBasal secretionCardiovascular diseaseT cellsKappaB activityFactor-kappaBHypertrophyCGB expressionBNP promoterPotent inducerAdult cardiomyocytesOctapeptide hormoneCalcium signalingUrocortin2 inhibits tumor growth via effects on vascularization and cell proliferation
Hao Z, Huang Y, Cleman J, Jovin IS, Vale WW, Bale TL, Giordano FJ. Urocortin2 inhibits tumor growth via effects on vascularization and cell proliferation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 3939-3944. PMID: 18308934, PMCID: PMC2268793, DOI: 10.1073/pnas.0712366105.Peer-Reviewed Original ResearchConceptsInhibits tumor growthTumor growthTumor vascularizationActivation of CRFR2Potential therapeutic roleTumor growth inhibitionTumor-suppressing effectsCRFR2 activationMeasurable tumorsTumor cell cyclingCell tumorsTherapeutic roleClinical malignancyUrocortin 2Peripheral tissuesCRFR2Ucn2Genetic deletionTissue vascularityDirect inhibitionVessel diameterCell proliferationVessel numberVascularizationTumorsEndothelial Expression of Beta‐1 Integrin Is Required for Embryonic Vascular Patterning and Postnatal Vascular Remodeling
lei L, Liu D, Huang Y, Jovin I, Shai S, Kyriakides T, Ross R, Giordano F. Endothelial Expression of Beta‐1 Integrin Is Required for Embryonic Vascular Patterning and Postnatal Vascular Remodeling. The FASEB Journal 2008, 22: 1122.11-1122.11. DOI: 10.1096/fasebj.22.1_supplement.1122.11.Peer-Reviewed Original ResearchVascular remodelingEndothelial expressionSevere fetal growth retardationFetal growth retardationCre/loxP techniqueAbnormal vascular remodelingSignificant clinical importancePostnatal vascular remodelingΒ1 subunit expressionΒ1 integrinBeta 1 integrinΒ1 integrin expressionBlood flowAdult miceClinical importanceSubunit expressionGlobal deletionPostnatal survivalGrowth retardationEndothelial cellsIntegrin expressionTime pointsHealing woundsSignificant functional effectsFunctional effectsEndothelial Expression of β1 Integrin Is Required for Embryonic Vascular Patterning and Postnatal Vascular Remodeling
Lei L, Liu D, Huang Y, Jovin I, Shai SY, Kyriakides T, Ross RS, Giordano FJ. Endothelial Expression of β1 Integrin Is Required for Embryonic Vascular Patterning and Postnatal Vascular Remodeling. Molecular And Cellular Biology 2008, 28: 794-802. PMID: 17984225, PMCID: PMC2223431, DOI: 10.1128/mcb.00443-07.Peer-Reviewed Original ResearchConceptsVascular patterningBeta1 integrinNormal vascular patterningEmbryonic vascular patterningBeta1 subunit expressionEmbryonic deathDevelopmental time pointsPostnatal vascular remodelingSignificant functional effectsBeta1 integrin expressionBiological processesVascular developmentExpression resultsDiminished vascularizationΒ1 integrinEmbryonic day 5Vascular remodelingCell growthGene deletionBeta1 subunitBeta1 geneIntegrins
2007
Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice
Murata T, Lin MI, Huang Y, Yu J, Bauer PM, Giordano FJ, Sessa WC. Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice. Journal Of Experimental Medicine 2007, 204: 2373-2382. PMID: 17893196, PMCID: PMC2118452, DOI: 10.1084/jem.20062340.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionRC miceCaveolin-1Endothelial cellsCav-1 KO miceEpithelial cellsCav-1-deficient miceSmooth muscle contractilityEndothelial NO synthase activationNitric oxide productionBronchiolar epithelial cellsNO synthase activationSmooth muscle cellsClear physiological evidenceCaveolin-1 knockout miceLack of rescueCav-1 expressionPulmonary dysfunctionPrincipal structural componentPulmonary arteryPulmonary defectsKO miceMuscle contractilityMyocardial hypertrophyAlveolar hyperplasiaHypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia.
Ziello J, Jovin I, Huang Y. Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. The Yale Journal Of Biology And Medicine 2007, 80: 51-60. PMID: 18160990, PMCID: PMC2140184.Peer-Reviewed Original ResearchConceptsHIF-1HIF-1 pathwayHypoxia-inducible factorDimeric protein complexProtein complexesCrucial physiological regulatorTranscription factorsTarget genesRegulatory pathwaysTranscriptional activityPrimary genesGenesPhysiological regulatorHomeostatic processesVessel proliferationLow oxygen concentrationsPathwayAnaerobic metabolismSmall moleculesCancerous cellsTherapeutic interventionsSpread of cancerProliferationTreatment of diseasesAngiogenic propertiesThe Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity*
Luan Y, Yu XP, Xu K, Ding B, Yu J, Huang Y, Yang N, Lengyel P, Di Cesare PE, Liu CJ. The Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity*. Journal Of Biological Chemistry 2007, 282: 16860-16870. PMID: 17439944, DOI: 10.1074/jbc.m610943200.Peer-Reviewed Original ResearchConceptsGene activationTranscription factorsRetinoblastoma proteinProtein-protein interactionsChromatin immunoprecipitation assaysMesenchymal cell lineSkeletal muscle myotubesP204 expressionP204 proteinCore-binding factor alpha1Numerous proteinsImmunoprecipitation assaysSuch mutantsOsteocalcin geneReporter geneGene expressionAntisense RNAMuscle myotubesOsteoblast differentiationCbfa1Factor alpha1ProteinEssential mediatorTernary complexCell linesEndothelial-Specific Expression of Mitochondrial Thioredoxin Improves Endothelial Cell Function and Reduces Atherosclerotic Lesions
Zhang H, Luo Y, Zhang W, He Y, Dai S, Zhang R, Huang Y, Bernatchez P, Giordano FJ, Shadel G, Sessa WC, Min W. Endothelial-Specific Expression of Mitochondrial Thioredoxin Improves Endothelial Cell Function and Reduces Atherosclerotic Lesions. American Journal Of Pathology 2007, 170: 1108-1120. PMID: 17322393, PMCID: PMC1864879, DOI: 10.2353/ajpath.2007.060960.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaApolipoproteins EAtherosclerosisCells, CulturedEndothelial CellsFlow CytometryImmunoblottingImmunohistochemistryMiceMice, TransgenicMicroscopy, ConfocalMitochondrial ProteinsNitric OxideReactive Oxygen SpeciesReverse Transcriptase Polymerase Chain ReactionThioredoxinsVasodilationConceptsTg miceAtherosclerotic lesionsOxidative stressNitric oxide levelsEC functionDeficient mouse modelEndothelial cell functionAtherosclerosis developmentEnhanced vasodilationVascular EC functionEndothelium functionApolipoprotein EControl littermatesMouse modelOxide levelsMice showCapacity of ECEndothelial-specific expressionEndothelial cellsCritical roleReactive oxygen speciesCell functionMiceTotal antioxidantsLesions
2006
p204 Protein Overcomes the Inhibition of the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes by Id Proteins*
Ding B, Liu CJ, Huang Y, Yu J, Kong W, Lengyel P. p204 Protein Overcomes the Inhibition of the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes by Id Proteins*. Journal Of Biological Chemistry 2006, 281: 14893-14906. PMID: 16556596, DOI: 10.1074/jbc.m511748200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell Line, TumorFeedback, PhysiologicalGATA4 Transcription FactorGene Expression RegulationHomeobox Protein Nkx-2.5Homeodomain ProteinsInhibitor of Differentiation Protein 1Inhibitor of Differentiation Protein 2Inhibitor of Differentiation ProteinsMiceMyocytes, CardiacNuclear ProteinsPhosphoproteinsTranscription FactorsTranscriptional ActivationConceptsD proteinsP204 proteinP19 cellsP19 murine embryonal carcinoma cellsEmbryonal carcinoma stem cellsNuclear export signalMurine embryonal carcinoma cellsP19 embryonal carcinoma stem cellsCardiac transcription factor GATA4Embryonal carcinoma cellsTranscription factor GATA4Carcinoma stem cellsExport signalSynergistic transactivationTranscription factorsNKX2.5 proteinPositive feedback loopCardiac myocytesDifferentiation proteinGATA4ProteinStem cellsDifferentiationP204Carcinoma cells