2023
Homeostatic, 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
2019
Genetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis
Price NL, Miguel V, Ding W, Singh AK, Malik S, Rotllan N, Moshnikova A, Toczek J, Zeiss C, Sadeghi MM, Arias N, Baldán Á, Andreev OA, Rodríguez-Puyol D, Bahal R, Reshetnyak YK, Suárez Y, Fernández-Hernando C, Lamas S. Genetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis. JCI Insight 2019, 4 PMID: 31613798, PMCID: PMC6948871, DOI: 10.1172/jci.insight.131102.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFatty AcidsFibrosisKidney DiseasesMaleMiceMice, Inbred C57BLMice, KnockoutMicroRNAsOxidation-ReductionConceptsFatty acid oxidationChronic kidney diseaseKidney diseaseDisease progressionMiR-33Bone marrow transplantExtent of fibrosisDevelopment of fibrosisAttractive therapeutic targetExpression of factorsNucleic acid inhibitorsMarrow transplantKidney fibrosisFibrotic kidneysMouse modelTherapeutic targetLipid metabolismPharmacological inhibitionFibrosisLipid accumulationDiseaseGenetic deficiencyProgressionKidneyAcid oxidation
2016
Rac2 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
2015
Interferon-&ggr;–Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients
Zhou J, Qin L, Yi T, Ali R, Li Q, Jiao Y, Li G, Tobiasova Z, Huang Y, Zhang J, Yun JJ, Sadeghi MM, Giordano FJ, Pober JS, Tellides G. Interferon-&ggr;–Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients. Circulation Research 2015, 117: 943-955. PMID: 26399469, PMCID: PMC4636943, DOI: 10.1161/circresaha.115.306932.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsAortic DiseasesApolipoproteins EAtherosclerosisCardiomyopathiesCardiovascular DiseasesDisease Models, AnimalFemaleGraft RejectionHeart TransplantationHemodynamicsHistocompatibility Antigens Class IIHyperlipidemiasInflammation MediatorsInterferon-gammaLymphocyte ActivationMaleMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutSignal TransductionTh1 CellsVentricular Dysfunction, LeftVentricular Function, LeftConceptsOrgan transplant recipientsCardiovascular diseaseTransplant recipientsEarly-onset cardiovascular diseaseEnd-stage organ failureNative coronary arteriesTh1-type cytokinesT helper cellsHost diseaseAlloimmune responseGraft rejectionAortic stiffeningOrgan failureVentricular dilatationAllogeneic graftsCardiovascular dysfunctionCoronary arteryAortic complianceRisk factorsEffective therapyCardiac contractilityMurine modelAnimal modelsSerological neutralizationImmune system
2013
Lipid lowering and imaging protease activation in atherosclerosis
Razavian M, Nie L, Challa A, Zhang J, Golestani R, Jung JJ, Robinson S, Sadeghi MM. Lipid lowering and imaging protease activation in atherosclerosis. Journal Of Nuclear Cardiology 2013, 21: 319-328. PMID: 24368425, PMCID: PMC3991560, DOI: 10.1007/s12350-013-9843-7.Peer-Reviewed Original ResearchConceptsHigh-fat dietLipid-lowering interventionsHFD groupPlaque inflammationAtherosclerotic miceMicroSPECT/CT imagingTotal blood cholesterolModern therapeutic approachesSmooth muscle αMMP tracerFat dietBlood cholesterolPlaque biologyTherapeutic approachesTracer uptakeMatrix metalloproteinaseTherapeutic interventionsAtherosclerosisActin expressionCT imagingMuscle αWeeksFenofibrateMiceInterventionTransmembrane 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
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
2010
Matrix Metalloproteinase Activation Predicts Amelioration of Remodeling After Dietary Modification in Injured Arteries
Tavakoli S, Razavian M, Zhang J, Nie L, Marfatia R, Dobrucki LW, Sinusas AJ, Robinson S, Edwards DS, Sadeghi MM. Matrix Metalloproteinase Activation Predicts Amelioration of Remodeling After Dietary Modification in Injured Arteries. Arteriosclerosis Thrombosis And Vascular Biology 2010, 31: 102-109. PMID: 20947820, PMCID: PMC3005135, DOI: 10.1161/atvbaha.110.216036.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins ECarotid Artery InjuriesCarotid Artery, CommonDietary FatsDisease Models, AnimalEnzyme ActivationFemaleInflammationMatrix Metalloproteinase InhibitorsMatrix MetalloproteinasesMiceMice, KnockoutMolecular ImagingProtease InhibitorsTime FactorsTomography, Emission-Computed, Single-PhotonX-Ray MicrotomographyConceptsHigh-fat dietMatrix metalloproteinase activationDietary modificationGroups of animalsMMP activationVascular remodelingMetalloproteinase activationCarotid artery wire injuryMonocyte/macrophage infiltrationMicro-single photon emissionCarotid neointima formationSingle photon emissionMacrophage infiltrationVascular injuryWire injuryNeointimal areaCarotid arteryNeointima formationInjured arteriesHistological analysisSurgeryWeeksNoninvasive imagingDietArteryMolecular Imaging of Matrix Metalloproteinase Activation to Predict Murine Aneurysm Expansion In Vivo
Razavian M, Zhang J, Nie L, Tavakoli S, Razavian N, Dobrucki LW, Sinusas AJ, Edwards DS, Azure M, Sadeghi MM. Molecular Imaging of Matrix Metalloproteinase Activation to Predict Murine Aneurysm Expansion In Vivo. Journal Of Nuclear Medicine 2010, 51: 1107-1115. PMID: 20554725, PMCID: PMC2908304, DOI: 10.2967/jnumed.110.075259.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins EArteriovenous FistulaAutoradiographyCarotid ArteriesCatalysisDisease ProgressionEnzyme ActivationImmunohistochemistryIndicators and ReagentsMatrix MetalloproteinasesMiceMice, KnockoutRadiopharmaceuticalsReverse Transcriptase Polymerase Chain ReactionSubstrate SpecificityTomography, Emission-ComputedTomography, Emission-Computed, Single-PhotonConceptsMatrix metalloproteinase activationMMP activationAneurysm inductionMetalloproteinase activationSPECT/CTCurrent imaging modalitiesPathogenesis of aneurysmsSpecific MMP inhibitorsGroups of animalsMMP tracerMolecular imagingArterial aneurysmsAneurysm expansionFocal uptakeDeficient miceCarotid aneurysmsCarotid arteryApolipoprotein ETracer uptakeAneurysmsMajor causeMMP inhibitorsVessel areaImaging modalitiesWk
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 processesWeeks