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
2020
Hydroxamate-Based Selective Macrophage Elastase (MMP-12) Inhibitors and Radiotracers for Molecular Imaging
Gona K, Toczek J, Ye Y, Sanzida N, Golbazi A, Boodagh P, Salarian M, Jung JJ, Rajendran S, Kukreja G, Wu TL, Devel L, Sadeghi MM. Hydroxamate-Based Selective Macrophage Elastase (MMP-12) Inhibitors and Radiotracers for Molecular Imaging. Journal Of Medicinal Chemistry 2020, 63: 15037-15049. PMID: 33206510, PMCID: PMC8010999, DOI: 10.1021/acs.jmedchem.0c01514.Peer-Reviewed Original ResearchConceptsAbdominal aortic aneurysmMMP-12 inhibitorsSelective MMP-12 inhibitorMurine abdominal aortic aneurysmsRadiochemical stabilityFast blood clearanceMolecular imagingAortic aneurysmAAA progressionMMP-12Blood clearanceUpregulated MMPsAortic regionElastase inhibitorLead tracerNovel familyRupture riskMacrophage elastaseInhibitorsSelectivitySpecific bindingSynthesisVivo competitionImaging
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 oxidationNovel Matrix Metalloproteinase 12 Selective Radiotracers for Vascular Molecular Imaging
Toczek J, Bordenave T, Gona K, Kim HY, Beau F, Georgiadis D, Correia I, Ye Y, Razavian M, Jung J, Lequin O, Dive V, Sadeghi MM, Devel L. Novel Matrix Metalloproteinase 12 Selective Radiotracers for Vascular Molecular Imaging. Journal Of Medicinal Chemistry 2019, 62: 9743-9752. PMID: 31603669, PMCID: PMC7054845, DOI: 10.1021/acs.jmedchem.9b01186.Peer-Reviewed Original ResearchConceptsAbdominal aortic aneurysmVascular molecular imagingMurine abdominal aortic aneurysmsMMP-12 gene expressionMatrix metalloproteinase-12Aortic aneurysmInflammatory diseasesAdjacent aortaH postinjectionMMP-12Blood clearanceMetalloproteinase-12Selective radiotracerFurther evaluationMMP-12 inhibitorsMouse bloodHigh uptakeAortaDiseaseMolecular imagingHuman metalloproteasesRadiotracer
2016
Optical imaging of MMP-12 active form in inflammation and aneurysm
Razavian M, Bordenave T, Georgiadis D, Beau F, Zhang J, Golestani R, Toczek J, Jung JJ, Ye Y, Kim HY, Han J, Dive V, Devel L, Sadeghi MM. Optical imaging of MMP-12 active form in inflammation and aneurysm. Scientific Reports 2016, 6: 38345. PMID: 27917892, PMCID: PMC5137160, DOI: 10.1038/srep38345.Peer-Reviewed Original ResearchMeSH KeywordsAneurysmAnimalsAntigens, DifferentiationCarotid ArteriesDisease Models, AnimalFluorescent DyesGene ExpressionHumansInflammationMacrophagesMatrix Metalloproteinase 12Matrix Metalloproteinase InhibitorsMiceMice, Inbred C57BLOptical ImagingPeptidesProtein BindingQuaternary Ammonium CompoundsSulfonic AcidsConceptsProbe 3Rac2 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 calcificationSynthesis and in Vitro and in Vivo Evaluation of MMP-12 Selective Optical Probes
Bordenave T, Helle M, Beau F, Georgiadis D, Tepshi L, Bernes M, Ye Y, Levenez L, Poquet E, Nozach H, Razavian M, Toczek J, Stura EA, Dive V, Sadeghi MM, Devel L. Synthesis and in Vitro and in Vivo Evaluation of MMP-12 Selective Optical Probes. Bioconjugate Chemistry 2016, 27: 2407-2417. PMID: 27564088, PMCID: PMC5100701, DOI: 10.1021/acs.bioconjchem.6b00377.Peer-Reviewed Original ResearchConceptsDye moietyLinker lengthSelective optical probeVivo performanceDye structureFirst crystal structureCyanine dyesHydrophilic characterSeries of tracersSelective probeReporter groupCrystal structureNovel seriesBlood clearance rateFluorescent probePseudopeptide inhibitorsWhole conjugateNet chargeMoietyCrystallographic structureSelectivity profileSmall peptidesOptical probeVivo behaviorVivo evaluationThe 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
2014
Imaging Vessel Wall Biology to Predict Outcome in Abdominal Aortic Aneurysm
Golestani R, Razavian M, Nie L, Zhang J, Jung JJ, Ye Y, de Roo M, Hilgerink K, Liu C, Robinson SP, Sadeghi MM. Imaging Vessel Wall Biology to Predict Outcome in Abdominal Aortic Aneurysm. Circulation Cardiovascular Imaging 2014, 8: &na;. PMID: 25550400, PMCID: PMC4284949, DOI: 10.1161/circimaging.114.002471.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticAorta, AbdominalAortic Aneurysm, AbdominalAortic RuptureAortographyBiomarkersDisease Models, AnimalDisease ProgressionEnzyme ActivationFeasibility StudiesMaleMatrix MetalloproteinasesMice, Inbred C57BLMice, TransgenicMolecular ImagingMultimodal ImagingPredictive Value of TestsRadiopharmaceuticalsRisk AssessmentRisk FactorsTime FactorsTomography, Emission-Computed, Single-PhotonTomography, X-Ray ComputedConceptsMicro-single photon emissionAngiotensin IIMatrix metalloproteinasesAortic diameterSuprarenal aortaCD68 expressionMMP activityPotential of MMPSaline-infused miceVessel wall inflammationAbdominal aortic aneurysmPrediction of outcomePhoton emissionRupture riskMurine AAAsAortic expansionRisk stratificationWall inflammationAortic aneurysmSpontaneous ruptureSmall aneurysmsMouse modelControl animalsTracer uptakeAbdominal aortic aneurysm (AAA) rupture risk
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
2005
Noninvasive Imaging of Angiogenesis With a 99mTc-Labeled Peptide Targeted at αvβ3 Integrin After Murine Hindlimb Ischemia
Hua J, Dobrucki LW, Sadeghi MM, Zhang J, Bourke BN, Cavaliere P, Song J, Chow C, Jahanshad N, van Royen N, Buschmann I, Madri JA, Mendizabal M, Sinusas AJ. Noninvasive Imaging of Angiogenesis With a 99mTc-Labeled Peptide Targeted at αvβ3 Integrin After Murine Hindlimb Ischemia. Circulation 2005, 111: 3255-3260. PMID: 15956134, DOI: 10.1161/circulationaha.104.485029.Peer-Reviewed Original Research