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
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 ResearchMeSH KeywordsAgedAnimalsAorta, AbdominalHomeostasisHumansMatrix Metalloproteinase 12Matrix MetalloproteinasesMicePhenotypePulse Wave AnalysisYoung AdultConceptsPulse 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
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
Novel 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 3Synthesis 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 evaluation