2024
Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis
Chanduri M, Kumar A, Weiss D, Emuna N, Barsukov I, Shi M, Tanaka K, Wang X, Datye A, Kanyo J, Collin F, Lam T, Schwarz U, Bai S, Nottoli T, Goult B, Humphrey J, Schwartz M. Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis. Science Advances 2024, 10: eadi6286. PMID: 39167642, PMCID: PMC11338229, DOI: 10.1126/sciadv.adi6286.Peer-Reviewed Original ResearchConceptsTissue mechanical homeostasisStiffness sensingExtracellular matrixTalin-1Mechanical homeostasisExtracellular matrix mechanicsIncreased cell spreadingCell spreadingTalinMutationsCellular sensingFibrillar collagenReduced axial stiffnessTissue mechanical propertiesMechanical propertiesAxial stiffnessCompliant substratesHomeostasisRupture pressureArp2/3ARPC5LStiffnessHomeostasis hypothesisResident cellsTissue stiffnessStiffening of the human proximal pulmonary artery with increasing age
Manning E, Mishall P, Ramachandra A, Hassab A, Lamy J, Peters D, Murphy T, Heerdt P, Singh I, Downie S, Choudhary G, Tellides G, Humphrey J. Stiffening of the human proximal pulmonary artery with increasing age. Physiological Reports 2024, 12: e16090. PMID: 38884325, PMCID: PMC11181131, DOI: 10.14814/phy2.16090.Peer-Reviewed Original ResearchConceptsProximal pulmonary arteriesPulmonary arteryAge-related stiffeningRight ventricular ejection fractionVentricular ejection fractionMean wall thicknessEjection fractionNo significant differenceSystemic circulationLuminal caliberDiffusing capacityArterial stiffeningIncreasing ageSignificant differenceDistensionArteryWall thicknessAdverse effectsWall strainVessel diameterCyclic biaxial strainOrgan donorsAgeMicrostructural remodelingHemodynamics and Wall Mechanics of Vascular Graft Failure
Szafron J, Heng E, Boyd J, Humphrey J, Marsden A. Hemodynamics and Wall Mechanics of Vascular Graft Failure. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: 1065-1085. PMID: 38572650, PMCID: PMC11043008, DOI: 10.1161/atvbaha.123.318239.Peer-Reviewed Original ResearchConceptsVascular graftsTissue-engineered vascular graftsWall mechanicsSolid mechanicsVascular graft failureLoad magnitudeMechanobiological processesLoadMechanobiological stimuliMechanosensitive signaling pathwaysBiomechanical stateWallGraft failureBiomechanical loadingCongenital heart surgeryCoronary artery bypass graftingEnd-organ dysfunctionGraft materialArtery bypass graftingFeedback loopComputational tools
2018
Strongly Coupled Morphological Features of Aortic Aneurysms Drive Intraluminal Thrombus
Bhagavan D, Di Achille P, Humphrey JD. Strongly Coupled Morphological Features of Aortic Aneurysms Drive Intraluminal Thrombus. Scientific Reports 2018, 8: 13273. PMID: 30185838, PMCID: PMC6125404, DOI: 10.1038/s41598-018-31637-6.Peer-Reviewed Original ResearchCompromised mechanical homeostasis in arterial aging and associated cardiovascular consequences
Ferruzzi J, Madziva D, Caulk AW, Tellides G, Humphrey JD. Compromised mechanical homeostasis in arterial aging and associated cardiovascular consequences. Biomechanics And Modeling In Mechanobiology 2018, 17: 1281-1295. PMID: 29754316, PMCID: PMC8344131, DOI: 10.1007/s10237-018-1026-7.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAorta, AbdominalAorta, ThoracicBiomechanical PhenomenaCardiovascular DiseasesCardiovascular SystemCarotid ArteriesCarotid Artery, CommonDiastoleDisease Models, AnimalElastinExtracellular Matrix ProteinsHemodynamicsHomeostasisHumansMaleMiceModels, CardiovascularPressureRecombinant ProteinsStress, MechanicalTime FactorsVascular StiffnessConceptsCentral arteriesMale wild-type miceArterial wallAberrant matrix remodelingCentral pulse pressureInfrarenal abdominal aortaCommon carotid arteryWild-type miceDiastolic functionCardiovascular consequencesCardiac massHemodynamic sequelaePulse pressureAbdominal aortaThoracic aortaArterial agingVascular agingCommon findingTreatment strategiesCarotid arteryArteryLeft ventricleCarotid vesselsCentral vesselsVivo axial stretch
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
Central Artery Stiffness in Hypertension and Aging
Humphrey JD, Harrison DG, Figueroa CA, Lacolley P, Laurent S. Central Artery Stiffness in Hypertension and Aging. Circulation Research 2016, 118: 379-381. PMID: 26846637, PMCID: PMC4745997, DOI: 10.1161/circresaha.115.307722.Peer-Reviewed Original Research
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 structureAortaMechanotransduction and extracellular matrix homeostasis
Humphrey JD, Dufresne ER, Schwartz MA. Mechanotransduction and extracellular matrix homeostasis. Nature Reviews Molecular Cell Biology 2014, 15: 802-812. PMID: 25355505, PMCID: PMC4513363, DOI: 10.1038/nrm3896.Peer-Reviewed Original ResearchA hypothesis-driven parametric study of effects of polymeric scaffold properties on tissue engineered neovessel formation
Miller KS, Khosravi R, Breuer CK, Humphrey JD. A hypothesis-driven parametric study of effects of polymeric scaffold properties on tissue engineered neovessel formation. Acta Biomaterialia 2014, 11: 283-294. PMID: 25288519, PMCID: PMC4256111, DOI: 10.1016/j.actbio.2014.09.046.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood VesselsCompressive StrengthComputer SimulationComputer-Aided DesignElastic ModulusEndothelial CellsEquipment DesignEquipment Failure AnalysisHardnessHumansMaterials TestingModels, ChemicalNeovascularization, PhysiologicPolymersTensile StrengthTissue EngineeringTissue ScaffoldsConceptsScaffold parametersMaterial propertiesScaffold structureParametric studyFibrous scaffoldsScaffold propertiesBurst pressureConstitutive relationsSuture retentionNeotissue developmentTissue engineeringMechanobiological cuesNeovessel developmentFiber diameterNew modeling frameworkExperimental search spaceVascular graftsOptimal combinationPropertiesKey propertiesModeling frameworkParametersNumber of parametersComputational modelNative propertiesDysfunctional 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