2024
SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts.
Goedeke L, Ma Y, Gaspar RC, Nasiri A, Lee J, Zhang D, Galsgaard KD, Hu X, Zhang J, Guerrera N, Li X, LaMoia T, Hubbard BT, Haedersdal S, Wu X, Stack J, Dufour S, Butrico GM, Kahn M, Perry RJ, Cline GW, Young LH, Shulman GI. SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts. J Clin Invest 2024, 134 PMID: 39680452, DOI: 10.1172/JCI176708.Peer-Reviewed Original ResearchMolecular Imaging of Collagen Turnover in Myocardial Infarction
Neishabouri A, Ghim M, Ahmad A, Kukreja G, Zhang Z, Li J, Salarian M, Toczek J, Gona K, Hedayatyanfard K, Zhang J, Huang H, Yu S, Sadeghi M. Molecular Imaging of Collagen Turnover in Myocardial Infarction. Journal Of Nuclear Cardiology 2024, 38: 101998. DOI: 10.1016/j.nuclcard.2024.101998.Peer-Reviewed Original ResearchA KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling
Deng H, Zhang J, Wang Y, Joshi D, Pi X, De Val S, Schwartz M. A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling. Nature Cardiovascular Research 2024, 3: 785-798. PMID: 39196179, DOI: 10.1038/s44161-024-00496-y.Peer-Reviewed Original ResearchFluid shear stressVascular remodelingOutward remodelingBone morphogenetic proteinShear stressMouse models of type 1Ischemic diseasesModels of type 1BMP-binding endothelial regulatorBlood flow recoveryType 2 diabetesPhysiological fluid shear stressPotential therapeutic approachBlocking antibodiesMouse modelSmad1/5 activationArterial remodelingTherapeutic approachesType 1Akt activationBlood flowEndothelial regulationSmad1/5Flow recoveryMorphogenetic proteinsDynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice
Boutagy N, Gamez-Mendez A, Fowler J, Zhang H, Chaube B, Esplugues E, Kuo A, Lee S, Horikami D, Zhang J, Citrin K, Singh A, Coon B, Lee M, Suarez Y, Fernandez-Hernando C, Sessa W. Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice. Journal Of Clinical Investigation 2024, 134: e170453. PMID: 38175710, PMCID: PMC10866653, DOI: 10.1172/jci170453.Peer-Reviewed Original Research
2023
Multimodality Imaging of Aortic Valve Calcification and Function in a Murine Model of Calcific Aortic Valve Disease and Bicuspid Aortic Valve
Ahmad A, Ghim M, Toczek J, Neishabouri A, Ojha D, Zhang Z, Gona K, Raza M, Jung J, Kukreja G, Zhang J, Guerrera N, Liu C, Sadeghi M. Multimodality Imaging of Aortic Valve Calcification and Function in a Murine Model of Calcific Aortic Valve Disease and Bicuspid Aortic Valve. Journal Of Nuclear Medicine 2023, 64: 1487-1494. PMID: 37321825, PMCID: PMC10478817, DOI: 10.2967/jnumed.123.265516.Peer-Reviewed Original ResearchConceptsF-NaF PET/CTCalcific aortic valve diseaseBicuspid aortic valvePET/CTAortic valve calcificationAortic valve diseaseAortic valveAortic stenosisValve calcificationValvular calcificationValve diseaseF-NaFSubset of miceTricuspid aortic valveDevelopment of calcificationSignificant correlationUnderwent echocardiographyMedical therapyHigh prevalencePreclinical modelsMurine modelTherapeutic interventionsAge groupsAutoradiography dataMultimodality imagingHigh-resolution visualization of pial surface vessels by flattened whole mount staining
Xu Y, Zhang J, Lee H, Zhang G, Bai Y, Simons M. High-resolution visualization of pial surface vessels by flattened whole mount staining. IScience 2023, 26: 106467. PMID: 37020957, PMCID: PMC10067958, DOI: 10.1016/j.isci.2023.106467.Peer-Reviewed Original ResearchBlood vesselsCerebral vasculatureWhole cerebral cortexCerebral blood vesselsParticular blood vesselCentral nervous system researchCLARITY technologyCerebral cortexStroke settingsCerebral vesselsWhole-mount techniqueDisease settingsEndothelial proliferationNervous system researchPostnatal developmentTherapeutic developmentWhole-mount stainingVasculatureVesselsMount stainingMount techniqueConfocal imagingNormal developmentHigh-resolution visualizationImagingHomeostatic, Non-Canonical Role of Macrophage Elastase in Vascular Integrity
Salarian M, Ghim M, Toczek J, Han J, Weiss D, Spronck B, Ramachandra A, Jung J, Kukreja G, Zhang J, Lakheram D, Kim S, Humphrey J, Sadeghi M. Homeostatic, Non-Canonical Role of Macrophage Elastase in Vascular Integrity. Circulation Research 2023, 132: 432-448. PMID: 36691905, PMCID: PMC9930896, DOI: 10.1161/circresaha.122.322096.Peer-Reviewed Original ResearchConceptsMMP-12 deficiencyAdverse aortic remodelingAbdominal aortic aneurysmAng IIAortic remodelingAortic aneurysmMMP-12Complement component 3 levelsNeutrophil extracellular traps markersAbdominal aortic aneurysm ruptureAortic aneurysm ruptureElastic lamina degradationPlasma complement componentsAortic ruptureC3 levelsComplement depositionPlasma C5aMore neutrophilsVascular remodelingAneurysm ruptureNeutrophil elastaseAortic integrityMatrix metalloproteinaseComplement inhibitorsNETosis pathway
2022
Fibronectin-Integrin α5 Signaling in Vascular Complications of Type 1 Diabetes.
Chen M, Hu R, Cavinato C, Zhuang ZW, Zhang J, Yun S, Fernandez Tussy P, Singh A, Murtada SI, Tanaka K, Liu M, Fernández-Hernando C, Humphrey JD, Schwartz MA. Fibronectin-Integrin α5 Signaling in Vascular Complications of Type 1 Diabetes. Diabetes 2022, 71: 2020-2033. PMID: 35771994, PMCID: PMC9450851, DOI: 10.2337/db21-0958.Peer-Reviewed Original ResearchConceptsVascular complicationsInjection of streptozotocinBlood flow recoveryHigh-fat dietType 1 diabetesInflammatory cell invasionIntegrin α5T1D miceVascular basement membraneVascular diseaseCarotid arteryHindlimb ischemiaMetalloproteinase expressionMain receptorType 1Plaque sizeBeneficial effectsEndothelial cellsMajor causeCell invasionExtracellular matrix proteinsHyperlipidemiaComplicationsBasement membraneT1DSyndecan-2 selectively regulates VEGF-induced vascular permeability
Corti F, Ristori E, Rivera-Molina F, Toomre D, Zhang J, Mihailovic J, Zhuang ZW, Simons M. Syndecan-2 selectively regulates VEGF-induced vascular permeability. Nature Cardiovascular Research 2022, 1: 518-528. PMID: 36212522, PMCID: PMC9544384, DOI: 10.1038/s44161-022-00064-2.Peer-Reviewed Original ResearchDifferential BMP Signaling Mediates the Interplay Between Genetics and Leaflet Numbers in Aortic Valve Calcification
Jung JJ, Ahmad AA, Rajendran S, Wei L, Zhang J, Toczek J, Nie L, Kukreja G, Salarian M, Gona K, Ghim M, Chakraborty R, Martin KA, Tellides G, Heistad D, Sadeghi MM. Differential BMP Signaling Mediates the Interplay Between Genetics and Leaflet Numbers in Aortic Valve Calcification. JACC Basic To Translational Science 2022, 7: 333-345. PMID: 35540096, PMCID: PMC9079798, DOI: 10.1016/j.jacbts.2021.12.006.Peer-Reviewed Original ResearchBicuspid aortic valveCalcific aortic valve diseaseAortic valve calcificationValve calcificationHuman Calcific Aortic Valve DiseaseAortic valve diseaseValve diseaseAortic valveCAVD progressionTherapeutic targetBone morphogenic proteinMorphogenic proteinMiceCalcificationDCBLD2StenosisExpressionLittermatesDiseaseBMP signalingProgression
2021
Fibronectin‐Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling
Budatha M, Zhang J, Schwartz MA. Fibronectin‐Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling. Journal Of The American Heart Association 2021, 10: e021160. PMID: 34472370, PMCID: PMC8649308, DOI: 10.1161/jaha.121.021160.Peer-Reviewed Original ResearchConceptsTransverse aortic constrictionPathological vascular remodelingVascular remodelingCarotid ligation modelPartial carotid ligation modelAortic constrictionInflammatory activationEndothelial cellsLigation modelArtery wall hypertrophyTransverse aortic constriction (TAC) modelHigh-fat dietIntegrin α5Aortic constriction modelWild-type miceBasement membranePartial carotid ligationVascular endothelial cellsProvisional matrix proteinsAcute atherosclerosisHyperlipidemic ApoEInflammatory markersLigation surgeryWall hypertrophyAcute modelComputed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm
Toczek J, Boodagh P, Sanzida N, Ghim M, Salarian M, Gona K, Kukreja G, Rajendran S, Wei L, Han J, Zhang J, Jung JJ, Graham M, Liu X, Sadeghi MM. Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm. Theranostics 2021, 11: 5876-5888. PMID: 33897887, PMCID: PMC8058712, DOI: 10.7150/thno.55106.Peer-Reviewed Original ResearchConceptsAbdominal aortic aneurysmExiTron nano 12000AAA outcomePhagocytic activityII infusionAng IIAortic aneurysmAortic wall enhancementAng II infusionCT enhancementAngiotensin II infusionRole of inflammationFeasibility of CTMacrophage phagocytic activityNon-invasive toolAAA inductionCD68 expressionModulatory interventionsMacrophage cell lineInflammatory signalsPatient managementVascular pathologyOutcome studiesAdventitial macrophagesComputed tomography
2018
Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation
Ye Y, Toczek J, Gona K, Kim HY, Han J, Razavian M, Golestani R, Zhang J, Wu TL, Ghosh M, Jung JJ, Sadeghi MM. Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation. Scientific Reports 2018, 8: 11647. PMID: 30076321, PMCID: PMC6076275, DOI: 10.1038/s41598-018-29941-2.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinasesMMP inhibitorsLung tissueTransgenic miceMMP activityHigh radiochemical purityHydroxamate MMP inhibitorsNumber of diseasesTissue remodelingSimilar inhibition potencyPotent inhibitionTherapySpecific bindingInhibitorsMolecular imagingImagingNovel arginineRadiochemical purityTissueHigh radiochemical yieldNew arginineEndothelial Cell Autonomous Role of Akt1
Lee MY, Gamez-Mendez A, Zhang J, Zhuang Z, Vinyard DJ, Kraehling J, Velazquez H, Brudvig GW, Kyriakides TR, Simons M, Sessa WC. Endothelial Cell Autonomous Role of Akt1. Arteriosclerosis Thrombosis And Vascular Biology 2018, 38: 870-879. PMID: 29449333, PMCID: PMC6503971, DOI: 10.1161/atvbaha.118.310748.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicBlood Flow VelocityBlood PressureDisease Models, AnimalEndothelial CellsHindlimbIschemiaMaleMice, KnockoutMuscle, SkeletalNeovascularization, PhysiologicNitric OxideNitric Oxide Synthase Type IIIPhosphorylationProto-Oncogene Proteins c-aktRegional Blood FlowSignal TransductionVasoconstrictionInhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis
Budatha M, Zhang J, Zhuang ZW, Yun S, Dahlman JE, Anderson DG, Schwartz MA. Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis. Journal Of The American Heart Association 2018, 7: e007501. PMID: 29382667, PMCID: PMC5850249, DOI: 10.1161/jaha.117.007501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesAtherosclerosisCyclic Nucleotide Phosphodiesterases, Type 4Disease Models, AnimalExtracellular MatrixFibronectinsFibrosisGenetic Predisposition to DiseaseHindlimbInflammation MediatorsIntegrin alpha2Integrin alpha5IschemiaLeukocytesMaleMatrix MetalloproteinasesMice, Inbred C57BLMice, Knockout, ApoEMuscle, SkeletalNeovascularization, PhysiologicNF-kappa BPhenotypePlaque, AtheroscleroticSignal TransductionVascular RemodelingConceptsEndothelial inflammatory activationAtherosclerotic plaque sizeInflammatory activationPlaque stabilityVascular remodelingEndothelial NF-κB activationSmooth muscle cell contentPlaque sizeFemoral artery ligationMuscle cell contentTreatment of atherosclerosisInflammatory gene expressionPotential therapeutic targetFibrous cap thicknessNF-κB activationSmaller atherosclerotic plaquesArtery ligationAortic rootHindlimb ischemiaCompensatory remodelingAtherosclerotic plaquesTherapeutic targetLeukocyte contentMetalloproteinase expressionEndothelial basement membrane
2017
Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta.
Misra A, Feng Z, Zhang J, Lou ZY, Greif DM. Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta. Journal Of Visualized Experiments 2017 PMID: 28930997, PMCID: PMC5752224, DOI: 10.3791/56039.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsAortic smooth muscle cellsPregnant micePharmacological agentsAortic wallAortaLarge arteriesAdult aortaMuscle cellsEndothelial cellsPathological modelsHypothesis-generating experimentsContinuous exposureCell explantsTissue explantsPathogenesisFate mappingSpecific gene targetsClonal analysisNormal developmentVivoGene targetsExtracellular matrixClonal architectureCellsVE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN
Conway DE, Coon BG, Budatha M, Arsenovic PT, Orsenigo F, Wessel F, Zhang J, Zhuang Z, Dejana E, Vestweber D, Schwartz MA. VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN. Current Biology 2017, 27: 2727. PMID: 28898639, PMCID: PMC5752114, DOI: 10.1016/j.cub.2017.08.064.Peer-Reviewed Original ResearchVE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN
Conway DE, Coon BG, Budatha M, Arsenovic PT, Orsenigo F, Wessel F, Zhang J, Zhuang Z, Dejana E, Vestweber D, Schwartz MA. VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN. Current Biology 2017, 27: 2219-2225.e5. PMID: 28712573, PMCID: PMC5667920, DOI: 10.1016/j.cub.2017.06.020.Peer-Reviewed Original ResearchConceptsSrc family kinasesProtein LGNCytoplasmic tyrosinesVE-cadherinVascular endothelial growth factor receptorVE-cadherin functionJunctional complexesRespective cytoplasmic domainsBlood vessel developmentVE-cadherin phosphorylationTransduce forcesTransduce signalsCytoplasmic domainFamily kinasesBlood vessel remodelingGrowth factor receptorVEGFR activationPECAM-1Stress responseComplex consistingFluid shear stressVessel developmentFlow-dependent vascular remodelingSpecific poolPhosphorylationPKN1 Directs Polarized RAB21 Vesicle Trafficking via RPH3A and Is Important for Neutrophil Adhesion and Ischemia-Reperfusion Injury
Yuan Q, Ren C, Xu W, Petri B, Zhang J, Zhang Y, Kubes P, Wu D, Tang W. PKN1 Directs Polarized RAB21 Vesicle Trafficking via RPH3A and Is Important for Neutrophil Adhesion and Ischemia-Reperfusion Injury. Cell Reports 2017, 19: 2586-2597. PMID: 28636945, PMCID: PMC5548392, DOI: 10.1016/j.celrep.2017.05.080.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCell AdhesionCell PolarityFemaleKidneyMaleMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsNeutrophilsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein Kinase CProtein Processing, Post-TranslationalProtein TransportRab GTP-Binding ProteinsReperfusion InjuryTransendothelial and Transepithelial MigrationTransport VesiclesVesicular Transport ProteinsConceptsTissue injuryNeutrophil adhesionRenal ischemia-reperfusion modelEndothelial cellsDecrease tissue injuryMyeloid-specific lossIschemia-reperfusion injuryIschemia-reperfusion modelInnate immune responseNeutrophil integrin activationInflammatory modelInflammatory responseImmune responseTherapeutic interventionsInjuryNeutrophilsRPH3AIntegrin activationCellsFGF-dependent metabolic control of vascular development
Yu P, Wilhelm K, Dubrac A, Tung JK, Alves TC, Fang JS, Xie Y, Zhu J, Chen Z, De Smet F, Zhang J, Jin SW, Sun L, Sun H, Kibbey RG, Hirschi KK, Hay N, Carmeliet P, Chittenden TW, Eichmann A, Potente M, Simons M. FGF-dependent metabolic control of vascular development. Nature 2017, 545: 224-228. PMID: 28467822, PMCID: PMC5427179, DOI: 10.1038/nature22322.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCell ProliferationEndothelial CellsFemaleFibroblast Growth FactorsGlycolysisHexokinaseLymphangiogenesisLymphatic VesselsMiceMice, Inbred C57BLNeovascularization, PhysiologicProto-Oncogene Proteins c-mycReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 3Signal Transduction