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
2014
Myh 11 R 247 C / R 247 C mutations increase thoracic aorta vulnerability to intramural damage despite a general biomechanical adaptivity
Bellini C, Wang S, Milewicz DM, Humphrey JD. Myh 11 R 247 C / R 247 C mutations increase thoracic aorta vulnerability to intramural damage despite a general biomechanical adaptivity. Journal Of Biomechanics 2014, 48: 113-121. PMID: 25433566, PMCID: PMC4283495, DOI: 10.1016/j.jbiomech.2014.10.031.Peer-Reviewed Original ResearchConceptsThoracic aortaSevere vascular phenotypeAortic aneurysmContractile proteinsLocalized poolsMedial smooth muscle cellsEpigenetic factorsGenetic studiesThoracic aortic diseaseThoracic aortic aneurysmSmooth muscle cellsSuch mutationsMutationsC mutationAortic dissectionAortic diseaseHistopathologic characteristicsMuscle cellsRisk factorsGlycosaminoglycans/proteoglycansNormal adaptationMouse modelNormal biomechanicsAortic structureAorta