2022
MicroRNAs in Mechanical Homeostasis
Herrera JA, Schwartz MA. MicroRNAs in Mechanical Homeostasis. Cold Spring Harbor Perspectives In Medicine 2022, 12: a041220. PMID: 35379658, PMCID: PMC9380736, DOI: 10.1101/cshperspect.a041220.Peer-Reviewed Original ResearchmTOR inhibition prevents angiotensin II–induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice
He C, Jiang B, Wang M, Ren P, Murtada SI, Caulk AW, Li G, Qin L, Assi R, Lovoulos CJ, Schwartz MA, Humphrey JD, Tellides G. mTOR inhibition prevents angiotensin II–induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice. JCI Insight 2022, 7: e155815. PMID: 35132962, PMCID: PMC8855820, DOI: 10.1172/jci.insight.155815.Peer-Reviewed Original ResearchConceptsApoE-deficient miceAngiotensin IIVascular wall cellsAortic tearAortic ruptureMTOR inhibitionSmooth muscle cell hypertrophyMatricellular proteinWall cellsSuprarenal abdominal aortaMuscle cell hypertrophyExtracellular matrix accumulationInhibition of mTORRole of mTORSubadventitial hematomaFree ruptureAortic dissectionAortic diseaseAortic aneurysmSignificant dissectionAbdominal aortaHemorrhagic lesionsExtensive dissectionMetalloproteinase expressionCell hypertrophy
2019
Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis
Chen PY, Qin L, Li G, Wang Z, Dahlman JE, Malagon-Lopez J, Gujja S, Cilfone N, Kauffman K, Sun L, Sun H, Zhang X, Aryal B, Canfran-Duque A, Liu R, Kusters P, Sehgal A, Jiao Y, Anderson D, Gulcher J, Fernandez-Hernando C, Lutgens E, Schwartz M, Pober J, Chittenden T, Tellides G, Simons M. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nature Metabolism 2019, 1: 912-926. PMID: 31572976, PMCID: PMC6767930, DOI: 10.1038/s42255-019-0102-3.Peer-Reviewed Original ResearchConceptsTGF-β signalingVascular inflammationDisease progressionPlaque growthProgressive vascular diseaseVessel wall inflammationChronic inflammatory responseSpecific therapeutic interventionsAtherosclerotic plaque growthHyperlipidemic micePlaque inflammationWall inflammationProinflammatory effectsVascular diseaseInflammatory responseVascular permeabilityAtherosclerotic plaquesAbnormal shear stressTherapeutic interventionsInflammationEndothelial TGFΒ signalingVessel wallAtherosclerosisLipid retention
2015
KLF4 is a key determinant in the development and progression of cerebral cavernous malformations
Cuttano R, Rudini N, Bravi L, Corada M, Giampietro C, Papa E, Morini MF, Maddaluno L, Baeyens N, Adams RH, Jain MK, Owens GK, Schwartz M, Lampugnani MG, Dejana E. KLF4 is a key determinant in the development and progression of cerebral cavernous malformations. EMBO Molecular Medicine 2015, 8: 6-24. PMID: 26612856, PMCID: PMC4718159, DOI: 10.15252/emmm.201505433.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 6Cell ProliferationDisease Models, AnimalDisease ProgressionEndothelial CellsHEK293 CellsHemangioma, Cavernous, Central Nervous SystemHumansKRIT1 ProteinKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMice, Inbred C57BLMice, KnockoutMicrotubule-Associated ProteinsMitogen-Activated Protein Kinase 7MutationProto-Oncogene ProteinsRNA InterferenceSignal TransductionSmad1 ProteinTransforming Growth Factor betaConceptsKruppel-like factor 4Cerebral cavernous malformationsEndothelial cellsCavernous malformationsFamilial cerebral cavernous malformationsCentral nervous systemDouble knockout miceGrowth factor-beta/bone morphogenetic protein signalingCerebral hemorrhageMouse mortalityPharmacological treatmentCurrent therapiesVascular malformationsKnockout miceTherapeutic targetNervous systemMesenchymal transitionKLF4 transcriptional activityMalformationsCCM3 genesFactor 4Function mutationsEndMTMorphogenetic protein signalingBone morphogenetic protein (BMP) signalingRole of Mechanotransduction in Vascular Biology
Humphrey JD, Schwartz MA, Tellides G, Milewicz DM. Role of Mechanotransduction in Vascular Biology. Circulation Research 2015, 116: 1448-1461. PMID: 25858068, PMCID: PMC4420625, DOI: 10.1161/circresaha.114.304936.Peer-Reviewed Original ResearchConceptsExtracellular matrixRole of mechanotransductionExtracellular matrix constituentsActomyosin filamentsMembrane receptorsDysfunctional mechanosensingVascular biologyAortic aneurysmNew therapeutic strategiesContractile proteinsThoracic aortic aneurysmIntramural cellsCellsMechanobiological processesMatrix constituentsAcute dissectionAortic cellsAortic diseaseMechanosensingTherapeutic strategiesHemodynamic loadGenesProgressive enlargementReceptorsMechanoregulation
2013
Flow-dependent cellular mechanotransduction in atherosclerosis
Conway DE, Schwartz MA. Flow-dependent cellular mechanotransduction in atherosclerosis. Journal Of Cell Science 2013, 126: 5101-5109. PMID: 24190880, PMCID: PMC3828588, DOI: 10.1242/jcs.138313.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisDisease ProgressionEndothelium, VascularHumansHypertensionMechanotransduction, CellularRisk FactorsStress, Mechanical
2012
p21-Activated kinase 4 promotes prostate cancer progression through CREB
Park M, Lee H, Lee C, You S, Kim D, Park B, Kang M, Heo W, Shin E, Schwartz M, Kim E. p21-Activated kinase 4 promotes prostate cancer progression through CREB. Oncogene 2012, 32: 2475-2482. PMID: 22710715, DOI: 10.1038/onc.2012.255.Peer-Reviewed Original ResearchConceptsP21-activated kinase 4Prostate cancer progressionProstate cancerCancer progressionLNCaP-FGC cellsPromising therapeutic targetKinase 4Prostate cancer cellsDU145 prostate cancer cellsSpecific protein kinase A (PKA) inhibitorProtein kinase A (PKA) inhibitorElevation of cAMPNeuroendocrine differentiationNude miceTherapeutic targetActive PAK4Downstream effector pathwaysTumor progressionDecreased expressionTumor formationCancerCancer cellsPC-3ProgressionEffector pathways
2009
Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function
Wu Y, Moissoglu K, Wang H, Wang X, Frierson HF, Schwartz MA, Theodorescu D. Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 5807-5812. PMID: 19321744, PMCID: PMC2667073, DOI: 10.1073/pnas.0810094106.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorDisease ProgressionGene Expression ProfilingGuanine Nucleotide Dissociation InhibitorsHumansImmunohistochemistryNeoplasm MetastasisPhosphorylationProtein BindingRho Guanine Nucleotide Dissociation Inhibitor betaRho-Specific Guanine Nucleotide Dissociation InhibitorsSrc-Family KinasesTumor Suppressor ProteinsUrinary Bladder NeoplasmsConceptsMetastasis suppressionSrc levelsSrc phosphorylation siteProtein interaction analysisMetastasis suppressor functionRhoGDI2 expressionSuppressor of metastasisGene expression profilingRhoGDI2 functionTyr-153Kinase bindsPhosphorylation sitesAmount of Rac1Expression profilingInteraction partnersSrc phosphorylationSrc inhibitorStable expressionBladder cancerSuppressor functionRhoGDI2Cancer cell linesCell membraneSrcPhosphorylation
2008
Endothelial Cell PECAM-1 Promotes Atherosclerotic Lesions in Areas of Disturbed Flow in ApoE-Deficient Mice
Harry BL, Sanders JM, Feaver RE, Lansey M, Deem TL, Zarbock A, Bruce AC, Pryor AW, Gelfand BD, Blackman BR, Schwartz MA, Ley K. Endothelial Cell PECAM-1 Promotes Atherosclerotic Lesions in Areas of Disturbed Flow in ApoE-Deficient Mice. Arteriosclerosis Thrombosis And Vascular Biology 2008, 28: 2003-2008. PMID: 18688018, PMCID: PMC2651147, DOI: 10.1161/atvbaha.108.164707.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, AbdominalAorta, ThoracicApolipoproteins EAtherosclerosisBone Marrow CellsBone Marrow TransplantationCells, CulturedDietary FatsDisease Models, AnimalDisease ProgressionEndothelial CellsHumansMacrophagesMiceMice, Inbred C57BLMice, KnockoutNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1Regional Blood FlowRNA InterferenceRNA, Small InterferingStress, MechanicalVascular Cell Adhesion Molecule-1ConceptsEndothelial PECAM-1PECAM-1Aortic archAbdominal aortaNF-kappaBVascular cell adhesion molecule-1 expressionCell adhesion molecule-1 expressionAdhesion molecule-1 expressionCell adhesion molecule-1ApoE-deficient miceAtherosclerotic lesion sizeBone marrow transplantationAtherosclerotic lesion formationMolecule-1 expressionVCAM-1 expressionAdhesion molecule-1Endothelial cell adhesion molecule-1NF-kappaB activityNuclear NF-kappaBDisturbed flowMarrow transplantationMacrophage infiltrationLesser curvatureWestern dietDeficient mice