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 imagingDisturbed flow increases endothelial inflammation and permeability via a Frizzled-4-β-catenin-dependent pathway
Rickman M, Ghim M, Pang K, von Huelsen Rocha A, Drudi E, Sureda-Vives M, Ayoub N, Tajadura-Ortega V, George S, Weinberg P, Warboys C. Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-β-catenin-dependent pathway. Journal Of Cell Science 2023, 136: jcs260449. PMID: 36846872, PMCID: PMC10112981, DOI: 10.1242/jcs.260449.Peer-Reviewed Original ResearchConceptsEndothelial dysfunctionEndothelial cellsFrizzled-4Β-cateninCultured human aortic endothelial cellsR-spondinsHuman aortic endothelial cellsPro-inflammatory genesEndothelial paracellular permeabilityDisturbed flowAortic endothelial cellsCultured endothelial cellsRole of WntEndothelial inflammationAortic archEarly atherogenesisCanonical Wnt pathwayDysfunctionReduced expressionWnt5a signalingParacellular permeabilityWnt pathwayInhibitionKnockdownExpressionHomeostatic, 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
Shear-mediated ALK5 expression regulates endothelial activation
Pang K, Ghim M, Sarathchandra P, Warboys C, Yacoub M, Chester A, Weinberg P. Shear-mediated ALK5 expression regulates endothelial activation. Biochemical And Biophysical Research Communications 2022, 642: 90-96. PMID: 36566567, DOI: 10.1016/j.bbrc.2022.12.058.Peer-Reviewed Original ResearchConceptsBlood flowCalcific aortic valve diseaseAortic valve diseaseHuman umbilical vein endothelial cell monolayersEndothelial-leukocyte adhesionALK5 kinase activityCardiovascular disease pathologyPotential therapeutic targetAortic valve tissueEndothelial dysfunctionValve diseaseALK5 expressionEndothelial activationFurther mechanistic investigationsEndothelial cell monolayersPorcine aortic valve tissuePathophysiological changesOvert diseaseAortic sidePathological changesTherapeutic targetVentricular sideLeukocyte adhesionMonocyte adhesionSmad2 phosphorylation
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
Visualization of three pathways for macromolecule transport across cultured endothelium and their modification by flow
Ghim M, Alpresa P, Yang S, Braakman S, Gray S, Sherwin S, van Reeuwijk M, Weinberg P. Visualization of three pathways for macromolecule transport across cultured endothelium and their modification by flow. AJP Heart And Circulatory Physiology 2017, 313: h959-h973. PMID: 28754719, PMCID: PMC5792200, DOI: 10.1152/ajpheart.00218.2017.Peer-Reviewed Original ResearchConceptsShear stressDifferent flow profilesType of flowTransverse stressesNumerical simulationsFlow profileFluid mechanical forcesShear profileShear vectorSolute transportTwo-pore theoryStatic conditionsFlowMacromolecule transportMechanical forcesTransportStressMicrovessel wallShearOrbital shakerStress metricsLong axisTracer distributionSimulations