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
Targeted Suppression of miRNA-33 Using pHLIP Improves Atherosclerosis Regression
Zhang X, Rotllan N, Canfrán-Duque A, Sun J, Toczek J, Moshnikova A, Malik S, Price NL, Araldi E, Zhong W, Sadeghi MM, Andreev OA, Bahal R, Reshetnyak YK, Suárez Y, Fernández-Hernando C. Targeted Suppression of miRNA-33 Using pHLIP Improves Atherosclerosis Regression. Circulation Research 2022, 131: 77-90. PMID: 35534923, PMCID: PMC9640270, DOI: 10.1161/circresaha.121.320296.Peer-Reviewed Original ResearchConceptsMiR-33Gene expressionNature of miRNAsSingle-cell RNA sequencing analysisSingle-cell RNA transcriptomicsAnti-miRNA technologiesRNA sequencing analysisExpression of miRNAsRNA transcriptomicsNew therapeutic opportunitiesEntire pathwayMiRNA therapeuticsAtherosclerotic plaque macrophagesHuman diseasesMiRNAsSequencing analysisSpecific tissuesMetabolic tissuesTargeted suppressionMiR-33 inhibitionProtective miRNAsNumerous diseasesPharmacological inhibitionLipid accumulationTarget effects
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
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-4
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 calcification
2011
Integrin-Targeted Imaging of Inflammation in Vascular Remodeling
Razavian M, Marfatia R, Mongue-Din H, Tavakoli S, Sinusas AJ, Zhang J, Nie L, Sadeghi MM. Integrin-Targeted Imaging of Inflammation in Vascular Remodeling. Arteriosclerosis Thrombosis And Vascular Biology 2011, 31: 2820-2826. PMID: 21940943, PMCID: PMC3228522, DOI: 10.1161/atvbaha.111.231654.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins ECalcium ChlorideCarotid Artery DiseasesCells, CulturedDisease Models, AnimalFemaleFluorescent DyesHumansInflammationIntegrin alphaVIntegrin alphaVbeta3Leukocytes, MononuclearMacrophagesMiceMice, KnockoutPeptides, CyclicRNA, MessengerTomography, Emission-Computed, Single-PhotonTomography, X-Ray ComputedConceptsVessel wall inflammationCarotid arteryWall inflammationTomography/CT imagingConsiderable macrophage infiltrationLeft carotid arteryMacrophage marker expressionReal-time polymerase chain reactionAdventitial exposureImaging of inflammationAntiinflammatory treatmentVascular eventsMacrophage infiltrationLeft carotidPolymerase chain reactionVascular diseaseContralateral arteryVascular remodelingHigh riskMurine carotid arteriesInflammationArteryFlow cytometryHuman monocytesMRNA expression