2017
mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice
Jiao Y, Li G, Li Q, Ali R, Qin L, Li W, Qyang Y, Greif DM, Geirsson A, Humphrey JD, Tellides G. mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice. Arteriosclerosis Thrombosis And Vascular Biology 2017, 37: 1657-1666. PMID: 28751568, PMCID: PMC5574180, DOI: 10.1161/atvbaha.117.309653.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicAortic DiseasesCell ProliferationCollagenElastinEverolimusFocal Adhesion Kinase 1Genetic Predisposition to DiseaseHumansImatinib MesylateMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Mechanotransduction, CellularMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesMuscle, Smooth, VascularPhenotypePhosphorylationProtein Kinase InhibitorsSirolimusTime FactorsTOR Serine-Threonine KinasesVascular StiffnessWilliams SyndromeConceptsElastin deficiencyCollagen accumulationArterial phenotypeNull miceGrowth factorSmooth muscle cell proliferationMuscle cell proliferationEarly postnatal deathInhibition of mTORAortic fibrosisAortic obstructionMedial thickeningAortic stiffeningNeonatal deathLuminal stenosisPharmacological blockadeAbsence of elastinThoracic aortaTherapeutic benefitJuvenile micePostnatal deathMTOR inhibitionAortaHeterozygous lossMice
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