2016
Differential Regulation of Macrophage Glucose Metabolism by Macrophage Colony-stimulating Factor and Granulocyte-Macrophage Colony-stimulating Factor: Implications for 18F FDG PET Imaging of Vessel Wall Inflammation.
Tavakoli S, Short JD, Downs K, Nguyen HN, Lai Y, Zhang W, Jerabek P, Goins B, Sadeghi MM, Asmis R. Differential Regulation of Macrophage Glucose Metabolism by Macrophage Colony-stimulating Factor and Granulocyte-Macrophage Colony-stimulating Factor: Implications for 18F FDG PET Imaging of Vessel Wall Inflammation. Radiology 2016, 283: 87-97. PMID: 27849433, PMCID: PMC5375627, DOI: 10.1148/radiol.2016160839.Peer-Reviewed Original ResearchConceptsM-CSFMurine atherosclerotic aortasStable isotope tracingActivation stateExtracellular acidification rateGM-CSFMitochondrial biogenesisMacrophage colony-stimulating factorGlycolytic enzymesGlucose fluxMurine peritoneal macrophagesDistinct activation statesGlycolytic pathwayGlucose transporterCritical glycolytic enzymeGlycolytic metabolismAcidification rateIsotope tracingIntermediary metabolitesGlucose uptakeImmunometabolic phenotypeMurine atherosclerotic plaquesCell culturesSimilar levelsOxidative metabolismRac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; Production
Ceneri N, Zhao L, Young BD, Healy A, Coskun S, Vasavada H, Yarovinsky TO, Ike K, Pardi R, Qin L, Qin L, Tellides G, Hirschi K, Meadows J, Soufer R, Chun HJ, Sadeghi M, Bender JR, Morrison AR. Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; Production. Arteriosclerosis Thrombosis And Vascular Biology 2016, 37: 328-340. PMID: 27834690, PMCID: PMC5269510, DOI: 10.1161/atvbaha.116.308507.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisCells, CulturedCoronary Artery DiseaseCoronary VesselsFemaleGenetic Predisposition to DiseaseHumansInflammation MediatorsInterleukin 1 Receptor Antagonist ProteinInterleukin-1betaMacrophagesMaleMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeuropeptidesPhenotypePlaque, AtheroscleroticPrognosisRac GTP-Binding ProteinsRac1 GTP-Binding ProteinSignal TransductionTransfectionUp-RegulationVascular CalcificationConceptsCoronary calcium burdenIL-1β expressionCalcium burdenSerum IL-1β levelsElevated IL-1βIL-1β levelsCoronary artery diseaseInterleukin-1β expressionCalcified coronary arteryCardiovascular deathCardiovascular eventsArtery diseaseIndependent predictorsClinical outcomesVascular calcificationCoronary arteryIL-1βPlaque calciumAtherosclerotic calcificationExperimental atherogenesisInflammatory regulatorsMacrophage interleukinAtherosclerotic plaquesTherapeutic targetProgressive calcificationThe neuropilin-like protein ESDN regulates insulin signaling and sensitivity
Li X, Jung JJ, Nie L, Razavian M, Zhang J, Samuel V, Sadeghi MM. The neuropilin-like protein ESDN regulates insulin signaling and sensitivity. AJP Heart And Circulatory Physiology 2016, 310: h1184-h1193. PMID: 26921437, PMCID: PMC4867389, DOI: 10.1152/ajpheart.00782.2015.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, CDAorta, ThoracicCell MovementCell ProliferationCells, CulturedDose-Response Relationship, DrugEnzyme ActivationFemaleGenotypeGRB10 Adaptor ProteinInsulinInsulin ResistanceMaleMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein KinasesMuscle, Smooth, VascularMyocytes, Smooth MuscleNeuropilinsPhenotypePhosphorylationProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionTime FactorsUbiquitinationConceptsSignal transductionNovel regulatorSmooth muscle cell-derived neuropilin-like proteinInsulin receptorInsulin receptor signal transductionMitogen-activated protein kinase activationSrc homology 2Novel regulatory mechanismReceptor signal transductionProtein kinase BInsulin signal transductionProtein kinase activationInsulin receptor phosphorylationPleckstrin homologyHomology 2Adaptor proteinTransmembrane proteinGrowth factor receptorKinase activationVascular smooth muscle cell proliferationRegulatory mechanismsKinase BInsulin signalingReceptor phosphorylationNovel therapeutic avenues
2013
Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis
Nie L, Guo X, Esmailzadeh L, Zhang J, Asadi A, Collinge M, Li X, Kim JD, Woolls M, Jin SW, Dubrac A, Eichmann A, Simons M, Bender JR, Sadeghi MM. Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis. Journal Of Clinical Investigation 2013, 123: 5082-5097. PMID: 24177422, PMCID: PMC3859420, DOI: 10.1172/jci67752.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBlood VesselsCadherinsCells, CulturedEar, ExternalEndothelium, VascularHindlimbHuman Umbilical Vein Endothelial CellsHumansIschemiaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutNeovascularization, PhysiologicNeuropilinsProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine Phosphatase, Non-Receptor Type 2Retinal VesselsRNA InterferenceRNA, Small InterferingVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ZebrafishZebrafish ProteinsConceptsSmooth muscle cell-derived neuropilin-like proteinAberrant blood vessel formationNormal vascular developmentProtein tyrosineTC-PTPTransmembrane proteinTherapeutic targetBlood vessel formationVEGF responseNegative regulatorDevelopmental angiogenesisVEGFR-2Vascular developmentAttractive therapeutic targetESDNAngiogenesis regulationVE-cadherinVessel formationEC proliferationComplex formationRegulatorProteinNeuropilin expressionVEGF receptorsEndothelial VEGF
2012
Molecular Imaging of Vascular Endothelial Growth Factor Receptors in Graft Arteriosclerosis
Zhang J, Razavian M, Tavakoli S, Nie L, Tellides G, Backer JM, Backer MV, Bender JR, Sadeghi MM. Molecular Imaging of Vascular Endothelial Growth Factor Receptors in Graft Arteriosclerosis. Arteriosclerosis Thrombosis And Vascular Biology 2012, 32: 1849-1855. PMID: 22723442, PMCID: PMC3401339, DOI: 10.1161/atvbaha.112.252510.Peer-Reviewed Original ResearchConceptsGraft arteriosclerosisArtery graftVascular remodelingAllogeneic human peripheral blood mononuclear cellsHuman coronary artery segmentsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsSevere combined immunodeficiency miceVEGF receptorsVascular endothelial growth factor receptorLate organ failureHuman coronary artery graftsSolid organ transplantationCoronary artery graftsEndothelial growth factor receptorBlood mononuclear cellsCoronary artery segmentsCombined immunodeficiency miceReceptor 2 expressionVEGF receptor-2 expressionMolecular imagingSignificant neointima formationVascular endothelial growth factor signalingVEGF receptor 1Growth factor receptor
2011
Integrin-Targeted Imaging of Inflammation in Vascular Remodeling
Razavian M, Marfatia R, Mongue-Din H, Tavakoli S, Sinusas AJ, Zhang J, Nie L, Sadeghi MM. Integrin-Targeted Imaging of Inflammation in Vascular Remodeling. Arteriosclerosis Thrombosis And Vascular Biology 2011, 31: 2820-2826. PMID: 21940943, PMCID: PMC3228522, DOI: 10.1161/atvbaha.111.231654.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins ECalcium ChlorideCarotid Artery DiseasesCells, CulturedDisease Models, AnimalFemaleFluorescent DyesHumansInflammationIntegrin alphaVIntegrin alphaVbeta3Leukocytes, MononuclearMacrophagesMiceMice, KnockoutPeptides, CyclicRNA, MessengerTomography, Emission-Computed, Single-PhotonTomography, X-Ray ComputedConceptsVessel wall inflammationCarotid arteryWall inflammationTomography/CT imagingConsiderable macrophage infiltrationLeft carotid arteryMacrophage marker expressionReal-time polymerase chain reactionAdventitial exposureImaging of inflammationAntiinflammatory treatmentVascular eventsMacrophage infiltrationLeft carotidPolymerase chain reactionVascular diseaseContralateral arteryVascular remodelingHigh riskMurine carotid arteriesInflammationArteryFlow cytometryHuman monocytesMRNA expression
2009
Endothelial and Smooth Muscle-derived Neuropilin-like Protein Regulates Platelet-derived Growth Factor Signaling in Human Vascular Smooth Muscle Cells by Modulating Receptor Ubiquitination*
Guo X, Nie L, Esmailzadeh L, Zhang J, Bender JR, Sadeghi MM. Endothelial and Smooth Muscle-derived Neuropilin-like Protein Regulates Platelet-derived Growth Factor Signaling in Human Vascular Smooth Muscle Cells by Modulating Receptor Ubiquitination*. Journal Of Biological Chemistry 2009, 284: 29376-29382. PMID: 19696027, PMCID: PMC2785569, DOI: 10.1074/jbc.m109.049684.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDown-RegulationHumansMembrane ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Muscle, Smooth, VascularMyocytes, Smooth MusclePhosphorylationPlatelet-Derived Growth FactorProto-Oncogene Proteins c-cblReceptor, Platelet-Derived Growth Factor betaSignal TransductionSrc-Family KinasesUbiquitin-Protein LigasesUbiquitinationConceptsPlatelet-derived growth factorSmooth muscle cell-derived neuropilin-like proteinPDGF receptorPlatelet-derived growth factor signalingPrototypic growth factorsE3 ubiquitin ligaseGrowth factor signalingExpression levelsPrimary human VSMCsHuman vascular smooth muscle cellsVascular smooth muscle cell growthReceptor ubiquitinationGrowth factorUbiquitin ligaseFactor signalingRNA interferenceC-CblVascular smooth muscle cellsSmooth muscle cell growthMuscle cell growthVSMC DNA synthesisUbiquitinationESDNHuman VSMCsSmooth muscle cells
2007
ESDN Is a Marker of Vascular Remodeling and Regulator of Cell Proliferation in Graft Arteriosclerosis
Sadeghi MM, Esmailzadeh L, Zhang J, Guo X, Asadi A, Krassilnikova S, Fassaei HR, Luo G, Al‐Lamki R, Takahashi T, Tellides G, Bender JR, Rodriguez ER. ESDN Is a Marker of Vascular Remodeling and Regulator of Cell Proliferation in Graft Arteriosclerosis. American Journal Of Transplantation 2007, 7: 2098-2105. PMID: 17697260, DOI: 10.1111/j.1600-6143.2007.01919.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCell ProliferationCells, CulturedCoronary Artery DiseaseCoronary VesselsDisease Models, AnimalHumansImmunohistochemistryMembrane ProteinsMiceMice, SCIDMuscle, Smooth, VascularReverse Transcriptase Polymerase Chain ReactionRNATissue TransplantationTransplantation, HomologousUp-RegulationConceptsGraft arteriosclerosisVascular remodelingCell proliferationSevere combined immunodeficient (SCID) miceInjury-induced vascular remodelingCombined Immunodeficient MiceHuman coronary arteriesVascular smooth muscle cell culturesVascular cell proliferationSmooth muscle cell culturesCell reconstitutionCoronary arteryImmunodeficient miceVSMC proliferationNormal arteriesArteryHuman coronaryMuscle cell culturesDiagnostic targetsHuman arteriesHigh levelsRemodelingSmooth muscle cell-derived neuropilin-like proteinArteriosclerosisProliferation
2006
HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced “inside-out” signaling to extracellular matrix by preventing RhoA activation
Xu H, Zeng L, Peng H, Chen S, Jones J, Chew TL, Sadeghi MM, Kanwar YS, Danesh FR. HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced “inside-out” signaling to extracellular matrix by preventing RhoA activation. American Journal Of Physiology. Renal Physiology 2006, 291: f995-f1004. PMID: 16774905, DOI: 10.1152/ajprenal.00092.2006.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsAnimalsCells, CulturedCollagen Type IVExtracellular MatrixFocal Adhesion Protein-Tyrosine KinasesHydroxymethylglutaryl-CoA Reductase InhibitorsIntegrin beta1Mesangial CellsMevalonic AcidPhosphorylationProlineRatsRhoA GTP-Binding ProteinSignal TransductionSimvastatinTritiumTyrosineVascular Endothelial Growth Factor AConceptsRhoA activationIntact actin cytoskeletonCell signaling cascadesPrecise signaling mechanismUnderlying molecular mechanismsActin cytoskeletonECM expansionMevalonate depletionSignaling cascadesIntegrin activationMevalonate pathwayECM accumulationMolecular mechanismsVEGF stimulationSignaling mechanismComplex biologyExtracellular matrixPleiotropic effectsAngiogenic polypeptideType IV collagen accumulationEndothelial cell permeabilityExtracellular matrix accumulationCell permeabilityGrowth factorPathological processes
2005
αvβ3‐Targeted detection of arteriopathy in transplanted human coronary arteries: an autoradiographic study
Zhang J, Krassilnikova S, Gharaei AA, Fassaei HR, Esmailzadeh L, Asadi A, Edwards DS, Harris TD, Azure M, Tellides G, Sinusas AJ, Zaret BL, Bender JR, Sadeghi MM. αvβ3‐Targeted detection of arteriopathy in transplanted human coronary arteries: an autoradiographic study. The FASEB Journal 2005, 19: 1857-1859. PMID: 16150802, DOI: 10.1096/fj.05-4130fje.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAutoradiographyCarotid Artery DiseasesCell MovementCell ProliferationCell TransplantationCells, CulturedChimeraCoronary VesselsDensitometryEndothelium, VascularHeart TransplantationHeterocyclic Compounds, 1-RingHumansImmunohistochemistryIntegrin alphaVbeta3Ki-67 AntigenLeukocytes, MononuclearMiceMice, SCIDMicroscopy, FluorescenceOrganometallic CompoundsRecombinant Fusion ProteinsTime FactorsTissue TransplantationUp-RegulationVascular DiseasesConceptsPeripheral blood mononuclear cellsGraft arteriopathyHuman coronary arteriesCoronary arteryAllogeneic human peripheral blood mononuclear cellsHuman/mouse chimeric modelAlphavbeta3 expressionHuman peripheral blood mononuclear cellsProliferative processesSevere combined immunodeficiency miceLate graft failureBlood mononuclear cellsCombined immunodeficiency miceAlphavbeta3 integrinSpecificity of uptakeCardiac transplantationConcentric narrowingGraft failureMononuclear cellsImmunodeficiency miceVascular remodelingNeointima formationNative aortaChimeric modelAutoradiographic study
2004
Detection of Injury-Induced Vascular Remodeling by Targeting Activated αvβ3 Integrin In Vivo
Sadeghi MM, Krassilnikova S, Zhang J, Gharaei AA, Fassaei HR, Esmailzadeh L, Kooshkabadi A, Edwards S, Yalamanchili P, Harris TD, Sinusas AJ, Zaret BL, Bender JR. Detection of Injury-Induced Vascular Remodeling by Targeting Activated αvβ3 Integrin In Vivo. Circulation 2004, 110: 84-90. PMID: 15210600, DOI: 10.1161/01.cir.0000133319.84326.70.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins EArterial Occlusive DiseasesCarbocyaninesCarotid StenosisCell ProliferationCells, CulturedEndothelium, VascularFemaleHeterocyclic Compounds, 1-RingHumansIntegrin alphaVbeta3MiceMice, KnockoutOrganometallic CompoundsRadioactive TracersSulfonamidesTomography, Emission-Computed, Single-PhotonConceptsCounts/pixelCarotid areaCarotid artery wire injuryEndothelial cellsIntegrin expressionInjury-induced remodelingCell proliferationDetection of injuryVascular cell proliferationCultured endothelial cellsCarotid injuryBeta3 integrin expressionWire injuryVascular proliferationRP748Vascular remodelingApolipoprotein EKi67 stainingRenal clearanceEC bindingProliferation indexSpecific radiotracersInjuryProliferative processesWeeksNoninvasive imaging of myocardial angiogenesis following experimental myocardial infarction
Meoli DF, Sadeghi MM, Krassilnikova S, Bourke BN, Giordano FJ, Dione DP, Su H, Edwards DS, Liu S, Harris TD, Madri JA, Zaret BL, Sinusas AJ. Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. Journal Of Clinical Investigation 2004, 113: 1684-1691. PMID: 15199403, PMCID: PMC420502, DOI: 10.1172/jci20352.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCoronary VesselsDiagnostic ImagingDogsEndothelial CellsEndothelium, VascularHemodynamicsIndium RadioisotopesIntegrin alphaVbeta3MaleMolecular StructureMyocardial InfarctionMyocardiumNeovascularization, PhysiologicQuinolonesRadiopharmaceuticalsRatsRats, Sprague-DawleyTechnetium Tc 99m SestamibiTomography, Emission-Computed, Single-PhotonConceptsMyocardial angiogenesisMyocardial infarctionRadiotracer uptakeInjury-induced angiogenesisChronic rat modelNoninvasive imaging strategiesTherapeutic myocardial angiogenesisExperimental myocardial infarctionFocal radiotracer uptakePotential novel targetSignificant clinical utilityAlphavbeta3 integrinRisk stratificationHistological evidenceHypoperfused regionsRat modelMyocardial radiotracer uptakeClinical utilityNoninvasive evaluationAngiogenic therapyCanine modelInfarct regionInfarctionNovel targetNoninvasive imagingVascular cell adhesion molecule-1-targeted detection of endothelial activation in human microvasculature
Sadeghi MM, Schechner JS, Krassilnikova S, Gharaei AA, Zhang J, Kirkiles-Smith N, Sinusas AJ, Zaret BL, Bender JR. Vascular cell adhesion molecule-1-targeted detection of endothelial activation in human microvasculature. Transplantation Proceedings 2004, 36: 1585-1591. PMID: 15251390, DOI: 10.1016/j.transproceed.2004.05.060.Peer-Reviewed Original ResearchConceptsChimeric human/mouse modelHuman/mouse modelHuman skin graftsEndothelial activationSkin graftsEndothelial cellsMouse modelIsotype-matched control antibodySCID/beige miceTumor necrosis factorEndothelial adhesion moleculesMurine VCAM-1Murine red blood cellsRed blood cellsHuman endothelial cellsControl antibodyInflammatory responseNecrosis factorBeige miceTc-99mVCAM-1Tissue vascularityMonoclonal antibodiesBlood cellsAdhesion molecules
2002
3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced proliferation of mesangial cells via modulation of Rho GTPase/ p21 signaling pathway: Implications for diabetic nephropathy
Danesh FR, Sadeghi MM, Amro N, Philips C, Zeng L, Lin S, Sahai A, Kanwar YS. 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced proliferation of mesangial cells via modulation of Rho GTPase/ p21 signaling pathway: Implications for diabetic nephropathy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 8301-8305. PMID: 12048257, PMCID: PMC123062, DOI: 10.1073/pnas.122228799.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell MembraneCells, CulturedCyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsDiabetic NephropathiesDNA ReplicationEnzyme InhibitorsGlomerular MesangiumGlucoseHydroxymethylglutaryl-CoA Reductase InhibitorsModels, BiologicalProtein PrenylationProtein TransportRatsRho GTP-Binding ProteinsSignal TransductionSimvastatinTransfectionConceptsDiabetic nephropathyMesangial cellsP21 protein expressionProtein expressionCdk2 kinase activityReductase inhibitorsExposure of MCsHigh glucose-induced proliferationProliferation of MCsUse of statinsHMG-CoA reductase inhibitorsLipid-lowering agentsCoronary heart diseaseCholesterol-lowering effectCoA reductase inhibitorsGlucose-induced proliferationGlomerular mesangial cellsRat mesangial cellsCholesterol-lowering propertiesStatin therapyHeart diseaseClinical dataCell cycle levelMC proliferationHigh glucose
2000
Simvastatin Modulates Cytokine-Mediated Endothelial Cell Adhesion Molecule Induction: Involvement of an Inhibitory G Protein
Sadeghi M, Collinge M, Pardi R, Bender J. Simvastatin Modulates Cytokine-Mediated Endothelial Cell Adhesion Molecule Induction: Involvement of an Inhibitory G Protein. The Journal Of Immunology 2000, 165: 2712-2718. PMID: 10946302, DOI: 10.4049/jimmunol.165.5.2712.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicBiological TransportCell Adhesion MoleculesCells, CulturedCholesterolCytokinesDrug SynergismE-SelectinEndothelium, VascularGene Expression RegulationGTP-Binding Protein alpha Subunits, Gi-GoHumansHydroxymethylglutaryl-CoA Reductase InhibitorsIntercellular Adhesion Molecule-1Interleukin-1NF-kappa BRNA, MessengerSignal TransductionSimvastatinSodium FluorideUmbilical VeinsVascular Cell Adhesion Molecule-1ConceptsEffect of simvastatinCytokine-induced expressionIL-1Endothelial CAMsEndothelial cell adhesion molecules E-selectinNF-kappaBProinflammatory cytokines IL-1Cell adhesion molecules E-selectinAdhesion molecules E-selectinPotent immune modulatorG protein activator NaFCytokines IL-1G protein-coupled pathwayInhibitory G proteinCytokine-mediated activationSelectin mRNA levelsBasal toneProinflammatory cytokinesGialpha proteinsImmune modulatorsTNF-alphaICAM-1Pertussis toxinE-selectinEndothelial response
1994
Heterogeneous activation thresholds to cytokines in genetically distinct endothelial cells: evidence for diverse transcriptional responses.
Bender JR, Sadeghi MM, Watson C, Pfau S, Pardi R. Heterogeneous activation thresholds to cytokines in genetically distinct endothelial cells: evidence for diverse transcriptional responses. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 3994-3998. PMID: 7513430, PMCID: PMC43709, DOI: 10.1073/pnas.91.9.3994.Peer-Reviewed Original Research