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 ResearchMeSH KeywordsAngiotensin IIAnimalsAorta, ThoracicFemaleMaleMiceMice, KnockoutReceptor, Angiotensin, Type 1Vascular RemodelingConceptsAngiotensin 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 pressure
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 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