2023
A novel human iPSC model of COL4A1/A2 small vessel disease unveils a key pathogenic role of matrix metalloproteinases
Al-Thani M, Goodwin-Trotman M, Bell S, Patel K, Fleming L, Vilain C, Abramowicz M, Allan S, Wang T, Cader M, Horsburgh K, Van Agtmael T, Sinha S, Markus H, Granata A. A novel human iPSC model of COL4A1/A2 small vessel disease unveils a key pathogenic role of matrix metalloproteinases. Stem Cell Reports 2023, 18: 2386-2399. PMID: 37977146, PMCID: PMC10724071, DOI: 10.1016/j.stemcr.2023.10.014.Peer-Reviewed Original ResearchConceptsSmall vessel diseaseMatrix metalloproteinasesVessel diseaseCerebral small vessel diseaseKey pathogenic roleEndothelial cell tight junctionsHuman iPSC modelSVD pathologyCo-culture modelLeading causePathogenic roleCell phenotypic changesExtracellular matrixParacrine actionCell tight junctionsMMP activityTherapeutic opportunitiesECM abnormalitiesCell defectsEndothelial cellsMural cellsSmall vesselsTight junctionsIPSC modelsDiseaseS-nitrosylation of EMMPRIN influences the migration of HSCs and MMP activity in liver fibrosis
Zhu X, Tang Z, Li W, Li X, Iwakiri Y, Liu F. S-nitrosylation of EMMPRIN influences the migration of HSCs and MMP activity in liver fibrosis. Acta Biochimica Et Biophysica Sinica 2023, 55: 1640-1649. PMID: 37700592, PMCID: PMC10577453, DOI: 10.3724/abbs.2023141.Peer-Reviewed Original ResearchConceptsExtracellular matrix metalloproteinase inducerLiver fibrosisLevels of EMMPRINMMP activitySinus epithelial cellsHSC migrationMatrix metalloproteinase inducerNormal control liversActivity of MMP2Matrix metalloproteinase activityS-nitrosylationStellate cell migrationHepatic stellate cell migrationTissue microarrayFibrotic liverFibrosisMouse liver tissueControl liversECM accumulationLiver tissueMetalloproteinase activityEMMPRIN mRNALiver areaEpithelial cellsProtein levelsPositron 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
Regional heterogeneity in determinants of atrial matrix remodeling and association with atrial fibrillation vulnerability postmyocardial infarction
Stacy MR, Lin BA, Thorn SL, Lobb DC, Maxfield MW, Novack C, Zellars KN, Freeburg L, Akar JG, Sinusas AJ, Spinale FG. Regional heterogeneity in determinants of atrial matrix remodeling and association with atrial fibrillation vulnerability postmyocardial infarction. Heart Rhythm 2022, 19: 847-855. PMID: 35066183, PMCID: PMC9064890, DOI: 10.1016/j.hrthm.2022.01.022.Peer-Reviewed Original ResearchConceptsAtrial fibrillationMyocardial infarctionRight atrial regionsAtrial regionsPost-MIMMP activityMatrix metalloproteinasesMMP/TIMP profilesNew-onset atrial fibrillationLeft atrial regionsMMP/TIMP expressionLeft atrial appendageMatrix remodelingElectrical stimulation protocolFibrillar collagen contentExtracellular matrix remodelingAF vulnerabilityTIMP profilesAtrial appendagePostmyocardial infarctionMyocardial substrateStimulation protocolNoninvasive molecular imagingTIMP expressionTissue inhibitor
2020
Dual Angiotensin Receptor-Neprilysin Inhibition With Sacubitril/Valsartan Attenuates Systolic Dysfunction in Experimental Doxorubicin-Induced Cardiotoxicity
Boutagy NE, Feher A, Pfau D, Liu Z, Guerrera NM, Freeburg LA, Womack SJ, Hoenes AC, Zeiss C, Young LH, Spinale FG, Sinusas AJ. Dual Angiotensin Receptor-Neprilysin Inhibition With Sacubitril/Valsartan Attenuates Systolic Dysfunction in Experimental Doxorubicin-Induced Cardiotoxicity. JACC CardioOncology 2020, 2: 774-787. PMID: 33437965, PMCID: PMC7799406, DOI: 10.1016/j.jaccao.2020.09.007.Peer-Reviewed Original ResearchSac/ValRodent modelsControl animalsMMP activityMatrix metalloproteinasesAngiotensin receptor blocker therapyAngiotensin receptor-neprilysin inhibitionTime-matched control animalsMyocardial MMP activityReceptor blocker therapySacubitril/valsartanHeart failure patientsVentricular ejection fractionAnthracycline-induced cardiotoxicityDoxorubicin-induced cardiotoxicityMale Wistar ratsSubgroup of animalsBlocker therapyAldosterone inhibitorsSystolic dysfunctionFailure patientsEjection fractionCardioprotective actionVentricular remodelingMyocardial infarction
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 arginine
2017
Preclinical 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
2015
Multimodality 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
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 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
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
Autoimmunity gene expression portrait: specific signature that intersects or differentiates between multiple sclerosis and systemic lupus erythematosus
MANDEL M, GUREVICH M, PAUZNER R, KAMINSKI N, ACHIRON A. Autoimmunity gene expression portrait: specific signature that intersects or differentiates between multiple sclerosis and systemic lupus erythematosus. Clinical & Experimental Immunology 2004, 138: 164-170. PMID: 15373920, PMCID: PMC1809188, DOI: 10.1111/j.1365-2249.2004.02587.x.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusPeripheral blood mononuclear cellsMultiple sclerosisHealthy subjectsAutoimmune signatureSLE patientsLupus erythematosusAutoimmune diseasesRelapsing-remitting MS patientsBlood mononuclear cellsMatrix metalloproteinase pathwayAdditional blood samplesDisease-specific signaturesDisease-associated signaturesTIMP1 gene expressionGene expression signaturesMS patientsMononuclear cellsSpecific therapyGene expression findingsMetalloproteinase pathwayNuclear autoantibodiesBlood samplesMMP activityPatientsEvaluation of myocardial matrix metalloproteinase (MMP) mediated post-MI remodeling with a novel radiolabeled MMP inhibitor
Su H, Spinale F, Dobrucki1 L, Chow C, Sweterlitsch S, Hu X, Bourke B, Cavaliere P, Hua J, Azure M, Edwards D, Sinusas A. Evaluation of myocardial matrix metalloproteinase (MMP) mediated post-MI remodeling with a novel radiolabeled MMP inhibitor. Journal Of Nuclear Cardiology 2004, 11: s20. DOI: 10.1016/j.nuclcard.2004.06.063.Peer-Reviewed Original ResearchMyocardial infarctionPost-MI remodelingPost-myocardial infarctionMMP activationMMP inhibitorsControl groupSitu zymographyMyocardial matrix metalloproteinasesMI regionMin post injectionControl miceMI miceVentricular remodelingPost-MIMI groupMurine modelNew therapiesMatrix metalloproteinaseMMP activityMatrix metalloproteinasesShort-axis slicesMI areaPost injectionMyocardial retentionMice
2000
Thrombospondin Type 1 Repeats Interact with Matrix Metalloproteinase 2 REGULATION OF METALLOPROTEINASE ACTIVITY*
Bein K, Simons M. Thrombospondin Type 1 Repeats Interact with Matrix Metalloproteinase 2 REGULATION OF METALLOPROTEINASE ACTIVITY*. Journal Of Biological Chemistry 2000, 275: 32167-32173. PMID: 10900205, DOI: 10.1074/jbc.m003834200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBlotting, WesternCatalytic DomainCattleCell LineCollagenasesEnzyme ActivationEnzyme PrecursorsHumansMatrix Metalloproteinase 2Matrix Metalloproteinase 3Matrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsPeptide FragmentsPrecipitin TestsProperdinProtein BindingProtein Structure, TertiaryRepetitive Sequences, Amino AcidSaccharomyces cerevisiaeThrombinThrombospondin 1ThrombospondinsTwo-Hybrid System TechniquesConceptsIntact thrombospondin-1Thrombospondin-1Ability of TSP1Matrix metalloproteinase-2Two-hybrid systemType 1 repeatsCatalytic domainCDNA clonesProtein interactionsThrombospondin type 1Terminal regionGelatin-binding domainAmino acidsInhibitors of angiogenesisCatalytic centerMMP activityTSP2Western blottingProteinTissue cultureClonesMapping sitesMetalloproteinase activityActivationMetalloproteinase-2
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