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
2021
Computed 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
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 calcificationMatrix metalloproteinase inhibitor, doxycycline and progression of calcific aortic valve disease in hyperlipidemic mice
Jung JJ, Razavian M, Kim HY, Ye Y, Golestani R, Toczek J, Zhang J, Sadeghi MM. Matrix metalloproteinase inhibitor, doxycycline and progression of calcific aortic valve disease in hyperlipidemic mice. Scientific Reports 2016, 6: 32659. PMID: 27619752, PMCID: PMC5020643, DOI: 10.1038/srep32659.Peer-Reviewed Original ResearchConceptsCalcific aortic valve diseaseAortic valve diseaseEffect of doxycyclineWestern dietCAVD progressionMatrix metalloproteinasesValve diseaseMicro-single photon emissionNonselective MMP inhibitorTherapeutic blood levelsLack of effectSingle photon emissionMatrix metalloproteinase inhibitorsGroups of animalsAortic stenosisMedical therapyHyperlipidemic miceEarly diseaseBlood levelsCommon causeTissue analysisMMP activationMMP inhibitionGelatinase activityDoxycycline
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 systemMultimodality and Molecular Imaging of Matrix Metalloproteinase Activation in Calcific Aortic Valve Disease
Jung JJ, Razavian M, Challa AA, Nie L, Golestani R, Zhang J, Ye Y, Russell KS, Robinson SP, Heistad DD, Sadeghi MM. Multimodality and Molecular Imaging of Matrix Metalloproteinase Activation in Calcific Aortic Valve Disease. Journal Of Nuclear Medicine 2015, 56: 933-938. PMID: 25908827, PMCID: PMC4454445, DOI: 10.2967/jnumed.114.152355.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortic ValveAortic Valve StenosisApolipoproteins EBicuspid Aortic Valve DiseaseCalcinosisDiet, High-FatEchocardiographyHeart Defects, CongenitalHeart Valve DiseasesHumansMatrix MetalloproteinasesMiceMice, TransgenicMolecular ImagingMultimodal ImagingTechnetiumTomography, Emission-Computed, Single-PhotonTomography, X-Ray ComputedConceptsCalcific aortic valve diseaseAortic valve diseaseMatrix metalloproteinasesWestern dietValve diseaseValvular inflammationMMP activityDevelopment of CAVDMedical therapeutic interventionsAortic valve areaSPECT/CT imagesWild-type miceMatrix metalloproteinase activationAortic stenosisMolecular imagingValvular calcificationControl miceCD68 expressionValve areaWD miceDeficient miceCommon causeApolipoprotein ECD68 stainingMurine model
2011
Atherosclerosis Plaque Heterogeneity and Response to Therapy Detected by In Vivo Molecular Imaging of Matrix Metalloproteinase Activation
Razavian M, Tavakoli S, Zhang J, Nie L, Dobrucki LW, Sinusas AJ, Azure M, Robinson S, Sadeghi MM. Atherosclerosis Plaque Heterogeneity and Response to Therapy Detected by In Vivo Molecular Imaging of Matrix Metalloproteinase Activation. Journal Of Nuclear Medicine 2011, 52: 1795-1802. PMID: 21969358, PMCID: PMC3235922, DOI: 10.2967/jnumed.111.092379.Peer-Reviewed Original ResearchConceptsHigh-fat dietSPECT/CTTracer uptakeMMP activationNormal chowMatrix metalloproteinasesApolipoprotein-deficient miceOil Red O stainingDevelopment of atherosclerosisMatrix metalloproteinase activationRed O stainingAtherosclerotic mouse aortasOil Red OHFD withdrawalMolecular imagingAreas of discordanceDietary modificationMacrophage infiltrationPlaque presenceMacrophage contentPlaque areaPlaque biologyAtherosclerotic plaquesMMP expressionMetalloproteinase activationIntegrin-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
2008
Molecular Imaging of Activated Matrix Metalloproteinases in Vascular Remodeling
Zhang J, Nie L, Razavian M, Ahmed M, Dobrucki LW, Asadi A, Edwards DS, Azure M, Sinusas AJ, Sadeghi MM. Molecular Imaging of Activated Matrix Metalloproteinases in Vascular Remodeling. Circulation 2008, 118: 1953-1960. PMID: 18936327, PMCID: PMC2637824, DOI: 10.1161/circulationaha.108.789743.Peer-Reviewed Original ResearchMeSH KeywordsAngioplasty, BalloonAnimalsApolipoproteins EAutoradiographyCarotid Artery InjuriesCarotid Artery, CommonDisease Models, AnimalFemaleFluorescent Antibody TechniqueIndiumMatrix Metalloproteinase 2Matrix Metalloproteinase 9MiceMice, Mutant StrainsSensitivity and SpecificityTomography, Emission-Computed, Single-PhotonConceptsVascular remodelingCarotid arteryCommon carotid artery injuryInjury-induced vascular remodelingCarotid wire injuryCarotid artery injuryMicroSPECT/CTMatrix metalloproteinase activationVessel wall areaArtery injuryCarotid injurySham surgerySignificant hyperplasiaContralateral arteryWire injuryFocal uptakeHyperplastic processesMicroSPECT imagingQuantitative autoradiographyTracer uptakeMetalloproteinase activationMMP activityArteryInjuryMatrix metalloproteinases
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