2024
Multiscale computational model of aortic remodeling following postnatal disruption of TGFβ signaling
Estrada A, Irons L, Tellides G, Humphrey J. Multiscale computational model of aortic remodeling following postnatal disruption of TGFβ signaling. Journal Of Biomechanics 2024, 169: 112152. PMID: 38763809, PMCID: PMC11141772, DOI: 10.1016/j.jbiomech.2024.112152.Peer-Reviewed Original ResearchAdult aortaTGFB signalingSmooth muscle cellsAortic remodelingCardiac-inducedMouse modelNormal mechanical loadingMuscle cellsPostnatal developmentHemodynamic loadNormal loadAortaMechanical homeostasisMechanical loadingMultiscale computational modelIncreasing loadLoadCell signalingGene productsStructural integrityA Systematic Comparison of Normal Structure and Function of the Greater Thoracic Vessels
Ramachandra A, Cavinato C, Humphrey J. A Systematic Comparison of Normal Structure and Function of the Greater Thoracic Vessels. Annals Of Biomedical Engineering 2024, 52: 958-966. PMID: 38227167, DOI: 10.1007/s10439-023-03432-6.Peer-Reviewed Original ResearchThoracic vesselsVena cavaThoracic aortaCongenital heart surgeryRight pulmonary arterySuperior vena cavaInferior vena cavaRight subclavian arteryThoracic inferior vena cavaWild-type miceAscending thoracic aortaDescending thoracic aortaPulmonary arterySubclavian arteryHeart surgerySurgical interventionVasoactive responsesVenous circulationThoracicCavaNormal structureAortaArteryBiomechanical propertiesVascular system
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 structureAortaDysfunctional Mechanosensing in Aneurysms
Humphrey JD, Milewicz DM, Tellides G, Schwartz MA. Dysfunctional Mechanosensing in Aneurysms. Science 2014, 344: 477-479. PMID: 24786066, PMCID: PMC4360903, DOI: 10.1126/science.1253026.Peer-Reviewed Original Research