2024
AT1b receptors contribute to regional disparities in angiotensin II mediated aortic remodelling in mice
Cavinato C, Spronck B, Caulk A, Murtada S, Humphrey J. AT1b receptors contribute to regional disparities in angiotensin II mediated aortic remodelling in mice. Journal Of The Royal Society Interface 2024, 21: 20240110. PMID: 39192727, PMCID: PMC11350382, DOI: 10.1098/rsif.2024.0110.Peer-Reviewed Original ResearchConceptsAngiotensin II infusionAT1B receptorsII infusionAngiotensin IIChronic angiotensin II infusionDays of angiotensin II infusionWild-typeAortas of WTSmooth muscle contractilityDescending thoracic aortaAngiotensin II signalingInflammatory cell responseRenin-angiotensin systemRegulating blood pressureAngII infusionAortic remodelingCell biological changesImmunohistological changesIndependent of sexMuscle contractilityMale miceMouse modelAbdominal aortaArterial remodelingBlood pressureCellular 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 stiffnessHemodynamics 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 toolsTissue engineered vascular grafts are resistant to the formation of dystrophic calcification
Turner M, Blum K, Watanabe T, Schwarz E, Nabavinia M, Leland J, Villarreal D, Schwartzman W, Chou T, Baker P, Matsumura G, Krishnamurthy R, Yates A, Hor K, Humphrey J, Marsden A, Stacy M, Shinoka T, Breuer C. Tissue engineered vascular grafts are resistant to the formation of dystrophic calcification. Nature Communications 2024, 15: 2187. PMID: 38467617, PMCID: PMC10928115, DOI: 10.1038/s41467-024-46431-4.Peer-Reviewed Original ResearchConceptsTissue-engineered vascular graftsTissue engineered vascular graftsVascular graftsCongenital heart surgeryComputational fluid dynamics simulationsFluid dynamics simulationsPolytetrafluoroethylene graftHeart surgeryDystrophic calcificationRetrospective clinical studyGraft complianceDegree of calcificationClinical studiesProsthetic biomaterialsBiomaterialsAnimal modelsPolytetrafluoroethyleneHemodynamic performanceNatural historyCalcificationGraftOvine modelVascular conduitsLong-term successSurgery
2018
Compromised 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 lossMiceComparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms
Bellini C, Bersi MR, Caulk AW, Ferruzzi J, Milewicz DM, Ramirez F, Rifkin DB, Tellides G, Yanagisawa H, Humphrey JD. Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms. Journal Of The Royal Society Interface 2017, 14: 20161036. PMID: 28490606, PMCID: PMC5454287, DOI: 10.1098/rsif.2016.1036.Peer-Reviewed Original ResearchConceptsGenetic mutationsExtracellular matrix proteinsTransmembrane receptorsCytoskeletal proteinsMatrix proteinsWild-type controlsBiomechanical phenotypeDysfunctional mechanosensingExtracellular matrixDiverse mouse modelsSmooth muscle cellsMutationsMuscle cellsProteinAorta of miceMurine modelCellsMechanosensingElastic fiber integrityMouse modelMechanoregulationStructural integrityPhenotypeIntracellularIntegrity
2016
Excessive Adventitial Remodeling Leads to Early Aortic Maladaptation in Angiotensin-Induced Hypertension
Bersi M, Bellini C, Wu J, Montaniel KR, Harrison DG, Humphrey JD. Excessive Adventitial Remodeling Leads to Early Aortic Maladaptation in Angiotensin-Induced Hypertension. Hypertension 2016, 67: 890-896. PMID: 27001298, PMCID: PMC4833633, DOI: 10.1161/hypertensionaha.115.06262.Peer-Reviewed Original ResearchConceptsAngiotensin II infusion modelAngiotensin-Induced HypertensionMost clinical assessmentsIntimal-medial thickeningWild-type miceNormal mechanical functionBlood pressureArterial stiffeningThoracic aortaInflammatory responseClinical assessmentEnd organsExuberant productionBlood flowCentral arteriesAdventitial collagenHypertensionWall stressExcessive accumulationInfusion modelMechanical functionWeeksCollagen resultsInflammationArteryCentral 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 properties