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 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/
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 ResearchMeSH KeywordsAngiotensin IIAnimalsAortaAortic Aneurysm, AbdominalApolipoproteins EDisease Models, AnimalMacrophagesMaleMiceMice, Inbred C57BLPhagocytesTomography, X-Ray ComputedConceptsAbdominal 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