2022
JAGGED1/NOTCH3 activation promotes aortic hypermuscularization and stenosis in elastin deficiency
Dave JM, Chakraborty R, Ntokou A, Saito J, Saddouk FZ, Feng Z, Misra A, Tellides G, Riemer RK, Urban Z, Kinnear C, Ellis J, Mital S, Mecham R, Martin KA, Greif DM. JAGGED1/NOTCH3 activation promotes aortic hypermuscularization and stenosis in elastin deficiency. Journal Of Clinical Investigation 2022, 132: e142338. PMID: 34990407, PMCID: PMC8884911, DOI: 10.1172/jci142338.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsSupravalvular aortic stenosisEndothelial cellsElastin insufficiencyObstructive arterial diseaseAortic smooth muscle cellsΓ-secretaseAortic vascular cellsPotential therapeutic targetNotch3 intracellular domainNotch ligand Jagged1Aortic stenosisArterial diseasePathological featuresPharmacological treatmentJag1 deletionLuminal obstructionMouse modelNotch3 activationTherapeutic targetSMC accumulationPathway upregulationAortic samplesMice displayNotch3 deletion
2018
Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells
Misra A, Feng Z, Chandran RR, Kabir I, Rotllan N, Aryal B, Sheikh AQ, Ding L, Qin L, Fernández-Hernando C, Tellides G, Greif DM. Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells. Nature Communications 2018, 9: 2073. PMID: 29802249, PMCID: PMC5970166, DOI: 10.1038/s41467-018-04447-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAtherosclerosisBone Marrow TransplantationCell MovementCell ProliferationCell TransdifferentiationCells, CulturedCholesterolDisease Models, AnimalFemaleHumansIntegrin beta3MacrophagesMaleMiceMice, Inbred C57BLMice, Knockout, ApoEMuscle, Smooth, VascularMyocytes, Smooth MusclePlaque, AtheroscleroticConceptsSmooth muscle cellsPre-existing smooth muscle cellsAtherosclerotic plaquesPlaque cellsToll-like receptor 4 expressionSmooth muscle-derived cellsBone marrow-derived cellsSingle smooth muscle cellsAtherosclerotic plaque cellsReceptor 4 expressionMarrow-derived cellsBone marrow resultsMuscle-derived cellsIntegrin β3 levelsMacrophage-like phenotypeCD36 levelsMarrow resultsSMC proliferationPlaque coresSMC progenitorsMuscle cellsIntegrin β3AtherogenesisPlaquesIntegrin beta3
2017
Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta.
Misra A, Feng Z, Zhang J, Lou ZY, Greif DM. Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta. Journal Of Visualized Experiments 2017 PMID: 28930997, PMCID: PMC5752224, DOI: 10.3791/56039.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsAortic smooth muscle cellsPregnant micePharmacological agentsAortic wallAortaLarge arteriesAdult aortaMuscle cellsEndothelial cellsPathological modelsHypothesis-generating experimentsContinuous exposureCell explantsTissue explantsPathogenesisFate mappingSpecific gene targetsClonal analysisNormal developmentVivoGene targetsExtracellular matrixClonal architectureCells
2016
Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis
Misra A, Sheikh AQ, Kumar A, Luo J, Zhang J, Hinton RB, Smoot L, Kaplan P, Urban Z, Qyang Y, Tellides G, Greif DM. Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis. Journal Of Experimental Medicine 2016, 213: 451-463. PMID: 26858344, PMCID: PMC4813675, DOI: 10.1084/jem.20150688.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsMutant miceTherapeutic strategiesAortic stenosis patientsAortic smooth muscle cellsSupravalvular aortic stenosisAttractive therapeutic strategyIntegrin β3 levelsAortic pathologyAortic stenosisStenosis patientsArterial diseaseLumen lossPathological featuresArterial mediaLarge arteriesAortic mediaElastin deficiencyPharmacological inhibitionMuscle cellsStenosisMicePathological stenosisExplant culturesSVAS patients