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 imagingHomeostatic, 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 pathwayPositron Emission Tomography Imaging of Vessel Wall Matrix Metalloproteinase Activity in Abdominal Aortic Aneurysm
Toczek J, Gona K, Liu Y, Ahmad A, Ghim M, Ojha D, Kukreja G, Salarian M, Luehmann H, Heo G, Guzman R, Chaar C, Tellides G, Hassab A, Ye Y, Shoghi K, Zayed M, Gropler R, Sadeghi M. Positron Emission Tomography Imaging of Vessel Wall Matrix Metalloproteinase Activity in Abdominal Aortic Aneurysm. Circulation Cardiovascular Imaging 2023, 16: e014615. PMID: 36649454, PMCID: PMC9858355, DOI: 10.1161/circimaging.122.014615.Peer-Reviewed Original ResearchConceptsAbdominal aortic aneurysmHuman aortic tissueMMP activityAortic tissueAortic aneurysmMMP inhibitorsMurine modelMatrix metalloproteinasesPositron emission tomography/Toxicology studiesAortic MMP activityPositron emission tomography radioligandAngiotensin II infusionEmission tomography/Murine abdominal aortic aneurysmsBroad-spectrum MMP inhibitorMatrix metalloproteinase activityPositron emission tomography (PET) tracerPositron emission tomography (PET) imagingEmission Tomography ImagingPositron emission tomographyEmission tomography tracerII infusionRisk stratificationTomography/
2022
Deletion of matrix metalloproteinase-12 compromises mechanical homeostasis and leads to an aged aortic phenotype in young mice
Spronck B, Ramachandra AB, Moriyama L, Toczek J, Han J, Sadeghi MM, Humphrey JD. Deletion of matrix metalloproteinase-12 compromises mechanical homeostasis and leads to an aged aortic phenotype in young mice. Journal Of Biomechanics 2022, 141: 111179. PMID: 35759974, PMCID: PMC9585962, DOI: 10.1016/j.jbiomech.2022.111179.Peer-Reviewed Original ResearchConceptsPulse wave velocityAortic phenotypeYoung miceAortic agingMMP-12Matrix metalloproteinasesMMP-12-deficient miceOld adult miceMatrix metalloproteinase-12Biomechanical propertiesAbdominal aortaArterial agingDeficient miceEnd organsBlood flowAdult miceCentral arteriesPercent changeMetalloproteinase-12MiceArterial wallAortaYoung adultsMatrix turnoverStrong proteolytic activity
2021
ESDN inhibits melanoma progression by blocking E-selectin expression in endothelial cells via STAT3
Coppo R, Orso F, Virga F, Dalmasso A, Baruffaldi D, Nie L, Clapero F, Dettori D, Quirico L, Grassi E, Defilippi P, Provero P, Valdembri D, Serini G, Sadeghi MM, Mazzone M, Taverna D. ESDN inhibits melanoma progression by blocking E-selectin expression in endothelial cells via STAT3. Cancer Letters 2021, 510: 13-23. PMID: 33862151, PMCID: PMC8581997, DOI: 10.1016/j.canlet.2021.04.005.Peer-Reviewed Original ResearchComputed 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 ResearchConceptsFatty 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
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 arginineMolecular imaging of calcific aortic valve disease
Jung JJ, Jadbabaie F, Sadeghi MM. Molecular imaging of calcific aortic valve disease. Journal Of Nuclear Cardiology 2018, 25: 1148-1155. PMID: 29359271, PMCID: PMC6054901, DOI: 10.1007/s12350-017-1158-7.Peer-Reviewed Original ResearchConceptsCalcific aortic valve diseaseAortic valve diseaseAortic stenosisValve diseaseSymptomatic aortic stenosisProgression of CAVDSubset of patientsRisk of complicationsMolecular imagingAsymptomatic patientsValvular calcificationDisease progressionFluoride PETTherapeutic interventionsClinical settingImaging protocolValvular biologyStenosisPatientsDiseaseCalcificationProgressionImagingEchocardiographyComplications
2017
Characterization of Macrophage Polarization States Using Combined Measurement of 2-Deoxyglucose and Glutamine Accumulation
Tavakoli S, Downs K, Short JD, Nguyen HN, Lai Y, Jerabek PA, Goins B, Toczek J, Sadeghi MM, Asmis R. Characterization of Macrophage Polarization States Using Combined Measurement of 2-Deoxyglucose and Glutamine Accumulation. Arteriosclerosis Thrombosis And Vascular Biology 2017, 37: 1840-1848. PMID: 28798141, PMCID: PMC8036006, DOI: 10.1161/atvbaha.117.308848.Peer-Reviewed Original ResearchConceptsMacrophage activation statesGlutamine accumulationVulnerable plaquesAtherosclerotic lesionsLow-density lipoprotein receptor-null miceF-fluorodeoxyglucose positron emission tomographyReceptor null miceF-fluorodeoxyglucose uptakeHigh-fat dietVessel wall inflammationMacrophage polarization stateEarly promising resultsActivation statePositron emission tomographyMurine peritoneal macrophagesProinflammatory stateInflammatory stateWall inflammationNecrosis factorF-fluorodeoxyglucosePolarization phenotypesInterleukin-4Preclinical Evaluation of RYM1, a Matrix Metalloproteinase–Targeted Tracer for Imaging Aneurysm
Toczek J, Ye Y, Gona K, Kim HY, Han J, Razavian M, Golestani R, Zhang J, Wu TL, Jung JJ, Sadeghi MM. Preclinical Evaluation of RYM1, a Matrix Metalloproteinase–Targeted Tracer for Imaging Aneurysm. Journal Of Nuclear Medicine 2017, 58: 1318-1323. PMID: 28360209, PMCID: PMC5537616, DOI: 10.2967/jnumed.116.188656.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinasesMMP activityCD68 expressionCarotid aneurysmsPreclinical evaluationAneurysm developmentAbdominal aortic aneurysm (AAA) developmentAortic MMP activityEarly vascular imagingAngiotensin II infusionLow blood levelsAortic aneurysm developmentSPECT/CT imagesReverse transcription-polymerase chain reactionSPECT/CT imagingRapid blood clearanceSmall-animal SPECT/CT imagingII infusionAortic uptakeAngiotensin IIBlood levelsPolymerase chain reactionAAA formationDeficient miceApolipoprotein E
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 3Differential 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 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 evaluationMatrix 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 activityDoxycyclineMatrix Metalloproteinase–Targeted Imaging of Lung Inflammation and Remodeling
Golestani R, Razavian M, Ye Y, Zhang J, Jung JJ, Toczek J, Gona K, Kim HY, Elias JA, Lee CG, Homer RJ, Sadeghi MM. Matrix Metalloproteinase–Targeted Imaging of Lung Inflammation and Remodeling. Journal Of Nuclear Medicine 2016, 58: 138-143. PMID: 27469361, PMCID: PMC5209638, DOI: 10.2967/jnumed.116.176198.Peer-Reviewed Original ResearchConceptsSmall-animal SPECT/CTSPECT/CTMatrix metalloproteinasesTg lungsLung inflammationTg miceIL-13 transgenic miceReal-time reverse transcription-polymerase chain reactionReverse transcription-polymerase chain reactionWild-type littermatesTranscription-polymerase chain reactionWild-type animalsMolecular imagingPulmonary inflammationPulmonary diseaseCD68 expressionLung diseasePolymerase chain reactionPulmonary pathologyEarly diagnosisInflammationMMP-13Transgenic miceMatrix metalloproteinaseMMP-12The 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