2024
Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis
Joshi D, Coon B, Chakraborty R, Deng H, Yang Z, Babar M, Fernandez-Tussy P, Meredith E, Attanasio J, Joshi N, Traylor J, Orr A, Fernandez-Hernando C, Libreros S, Schwartz M. Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis. Nature Cardiovascular Research 2024, 3: 1035-1048. PMID: 39232138, PMCID: PMC11399086, DOI: 10.1038/s44161-024-00522-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCadherin Related ProteinsCadherinsDisease Models, AnimalEndothelial CellsHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiceMice, Inbred C57BLMice, KnockoutPlaque, AtheroscleroticReceptors, NotchSignal TransductionConceptsAtherosclerotic cardiovascular diseaseIntracellular domainNotch intracellular domainTranscription factor KLF2Mechanisms of vascular inflammationAnti-inflammatory programVascular endothelial cellsHost defenseCleavage resultsAntibody blockadeGenetic deletionVascular inflammationViral infectionImmune systemEndothelial cellsCardiovascular diseasePromote atherosclerosisBlood flowKLF2KLF4Suppressive signalsEndotheliumMechanistic studiesControversy in mechanotransduction – the role of endothelial cell–cell junctions in fluid shear stress sensing
X S, Aitken C, Mehta V, Tardajos-Ayllon B, Serbanovic-Canic J, Zhu J, Miao B, Tzima E, Evans P, Fang Y, Schwartz M. Controversy in mechanotransduction – the role of endothelial cell–cell junctions in fluid shear stress sensing. Journal Of Cell Science 2024, 137: jcs262348. PMID: 39143856, PMCID: PMC11423816, DOI: 10.1242/jcs.262348.Peer-Reviewed Original ResearchShear stress sensingFluid shear stressFluid flowCell-cell contactShear stressCell-cell adhesionStress sensingCell-cell junctionsEndothelial cell-cell junctionsEC alignmentRegulates vascular developmentAdhesion receptorsCell typesEndothelial cellsFlowSingle cellsVascular developmentShearAdhesionContactCellular 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 stiffnessA KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling
Deng H, Zhang J, Wang Y, Joshi D, Pi X, De Val S, Schwartz M. A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling. Nature Cardiovascular Research 2024, 3: 785-798. PMID: 39196179, DOI: 10.1038/s44161-024-00496-y.Peer-Reviewed Original ResearchFluid shear stressVascular remodelingOutward remodelingBone morphogenetic proteinShear stressMouse models of type 1Ischemic diseasesModels of type 1BMP-binding endothelial regulatorBlood flow recoveryType 2 diabetesPhysiological fluid shear stressPotential therapeutic approachBlocking antibodiesMouse modelSmad1/5 activationArterial remodelingTherapeutic approachesType 1Akt activationBlood flowEndothelial regulationSmad1/5Flow recoveryMorphogenetic proteinsLatrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions
Tanaka K, Chen M, Prendergast A, Zhuang Z, Nasiri A, Joshi D, Hintzen J, Chung M, Kumar A, Mani A, Koleske A, Crawford J, Nicoli S, Schwartz M. Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions. The EMBO Journal 2024, 43: 3175-3191. PMID: 38886581, PMCID: PMC11294477, DOI: 10.1038/s44318-024-00142-0.Peer-Reviewed Original ResearchLatrophilin-2Affinity purification methodCell-cell junctionsHuman genetic dataPECAM-1SiRNA screenGenetic dataEndothelial cell response to fluid shear stressGA proteinsDownstream eventsEndothelial-specific knockoutG-proteinActivity assayShear stress mechanotransductionPlexin-D1Endothelial signalingJunctional complexesPurification methodVE-cadherinResponse to fluid shear stressVascular developmentGA residuesEndothelial junctionsGPCRsVEGF receptorsFocal adhesion-derived liquid-liquid phase separations regulate mRNA translation.
Kumar A, Tanaka K, Schwartz MA. Focal adhesion-derived liquid-liquid phase separations regulate mRNA translation. BioRxiv 2024 PMID: 38045367, DOI: 10.1101/2023.11.22.568289.Peer-Reviewed Original ResearchAfadin–nectin forces its way to the front
Sebbagh M, Schwartz M. Afadin–nectin forces its way to the front. Journal Of Cell Biology 2024, 223: e202403177. PMID: 38563860, PMCID: PMC10988649, DOI: 10.1083/jcb.202403177.Peer-Reviewed Original ResearchDysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities
Stroope C, Nettersheim F, Coon B, Finney A, Schwartz M, Ley K, Rom O, Yurdagul A. Dysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities. Nature Metabolism 2024, 6: 617-638. PMID: 38532071, PMCID: PMC11055680, DOI: 10.1038/s42255-024-01015-w.Peer-Reviewed Original ResearchDysregulated cellular metabolismAtherosclerotic cardiovascular diseaseLesional cellsAtherosclerosis progressionCardiovascular diseaseDysregulation of cellular metabolismVascular smooth muscle cellsProgression of atherosclerotic cardiovascular diseaseSmooth muscle cellsCellular metabolismT cellsMetabolic alterationsMuscle cellsMetabolic dysregulationCardiovascular therapeuticsTherapeutic opportunitiesEndothelial cellsTherapeutic targetMetabolic cross-talkAtherosclerosisCellsDiseaseDysregulationCross-talkMetabolismMechanosensing through talin 1 contributes to tissue mechanical homeostasis.
Chanduri MVL, Kumar A, Weiss D, Emuna N, Barsukov I, Shi M, Tanaka K, Wang X, Datye A, Kanyo J, Collin F, Lam T, Schwarz UD, Bai S, Nottoli T, Goult BT, Humphrey JD, Schwartz MA. Mechanosensing through talin 1 contributes to tissue mechanical homeostasis. BioRxiv 2024 PMID: 38328095, DOI: 10.1101/2023.09.03.556084.Peer-Reviewed Original Research In PressGamma protocadherins in vascular endothelial cells inhibit Klf2/4 to promote atherosclerosis.
Joshi D, Coon BG, Chakraborty R, Deng H, Fernandez-Tussy P, Meredith E, Traylor JG Jr, Orr AW, Fernandez-Hernando C, Schwartz MA. Gamma protocadherins in vascular endothelial cells inhibit Klf2/4 to promote atherosclerosis. BioRxiv 2024 PMID: 38293157, DOI: 10.1101/2024.01.16.575958.Peer-Reviewed Original Research In Press
2023
Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton
Amiri S, Muresan C, Shang X, Huet-Calderwood C, Schwartz M, Calderwood D, Murrell M. Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton. Nature Communications 2023, 14: 8011. PMID: 38049429, PMCID: PMC10695988, DOI: 10.1038/s41467-023-43612-5.Peer-Reviewed Original ResearchConceptsF-actin architectureStress fibersCortical actinActin cytoskeletonMolecular tension sensorsF-actin stress fibersF-actin cytoskeletonFilamentous actin cytoskeletonMechanical forcesTension sensorCell divisionCytoskeletonCell migrationExtracellular matrixMyosin inhibitionActinDirection of stretchCellsCell axisUniaxial stretchStretchFRETSMAD4 maintains the fluid shear stress set point to protect against arterial-venous malformations
Banerjee K, Lin Y, Gahn J, Cordero J, Gupta P, Mohamed I, Graupera M, Dobreva G, Schwartz M, Ola R. SMAD4 maintains the fluid shear stress set point to protect against arterial-venous malformations. Journal Of Clinical Investigation 2023, 133: e168352. PMID: 37490341, PMCID: PMC10503796, DOI: 10.1172/jci168352.Peer-Reviewed Original ResearchConceptsActivin-like kinase 1Fluid shear stressSMAD family member 4Arterial identityCyclin-dependent kinase inhibitors Cdkn2aVascular network formsEndothelial cellsVascular stabilitySensitivity of ECsBMP signalsPI3K/AktFamily member 4Downstream effectorsProtein 9Kinase 1Vascular developmentBone morphogenic protein 9Mechanism of synergyMorphological responsesSMAD4 deletionEC proliferationMember 4The importance of character development in scientific research
Schwartz M, Yap A. The importance of character development in scientific research. Journal Of Cell Science 2023, 136 PMID: 37403645, DOI: 10.1242/jcs.261405.Peer-Reviewed Original ResearchMechanisms of endothelial flow sensing
Aitken C, Mehta V, Schwartz M, Tzima E. Mechanisms of endothelial flow sensing. Nature Cardiovascular Research 2023, 2: 517-529. PMID: 39195881, DOI: 10.1038/s44161-023-00276-0.Peer-Reviewed Original ResearchAltered Integrin Signaling in Thoracic Aortopathy
Humphrey J, Schwartz M. Altered Integrin Signaling in Thoracic Aortopathy. Arteriosclerosis Thrombosis And Vascular Biology 2023, 43: 1154-1156. PMID: 37165879, DOI: 10.1161/atvbaha.123.319404.Commentaries, Editorials and LettersFN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome
Chen M, Cavinato C, Hansen J, Tanaka K, Ren P, Hassab A, Li D, Youshao E, Tellides G, Iyengar R, Humphrey J, Schwartz M. FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome. Arteriosclerosis Thrombosis And Vascular Biology 2023, 43: e132-e150. PMID: 36994727, PMCID: PMC10133209, DOI: 10.1161/atvbaha.123.319120.Peer-Reviewed Original ResearchConceptsContractile gene expressionSmooth muscle cellsGene expressionMgR miceWild-type smooth muscle cellsMarfan miceAortic aneurysmMouse modelMarfan syndromeMouse aortic smooth muscle cellsPathogenesis of TAACytoplasmic domainVascular smooth muscle cellsThoracic aortic aneurysmAortic smooth muscle cellsCultured smooth muscle cellsNF-kB activationNF-kB inhibitionMolecular mechanismsIntegrin α2ECM remodelingElastic fiber integrityPhenotypic modulationMarfan's aneurysmsMgR/TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity
Gallego-Paez L, Edwards W, Chanduri M, Guo Y, Koorman T, Lee C, Grexa N, Derksen P, Yan J, Schwartz M, Mauer J, Goult B. TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity. Journal Of Cell Biology 2023, 222: e202209010. PMID: 36880935, PMCID: PMC9997659, DOI: 10.1083/jcb.202209010.Peer-Reviewed Original ResearchConceptsExon 17bTerminal FERM domainVinculin bindingFERM domainSwitch domainAdhesion dynamicsCassette exonsSplicing analysisAdapter proteinTLN1Single isoformIsoform switchTalin-1Amino acidsFrame insertionExonsBiochemical analysisIsoformsProteinExon 17CytoskeletonGenesMechanotransductionDomainIntegrins
2022
Integrin αIIbβ3 intermediates: From molecular dynamics to adhesion assembly
Tong D, Soley N, Kolasangiani R, Schwartz M, Bidone T. Integrin αIIbβ3 intermediates: From molecular dynamics to adhesion assembly. Biophysical Journal 2022, 122: 533-543. PMID: 36566352, PMCID: PMC9941721, DOI: 10.1016/j.bpj.2022.12.032.Peer-Reviewed Original ResearchIntegrin Conformational Dynamics and Mechanotransduction
Kolasangiani R, Bidone T, Schwartz M. Integrin Conformational Dynamics and Mechanotransduction. Cells 2022, 11: 3584. PMID: 36429013, PMCID: PMC9688440, DOI: 10.3390/cells11223584.Peer-Reviewed Original ResearchConceptsCell-cell adhesionCell-extracellular matrixExtracellular ligandsIntegrin affinityConformational dynamicsIntegrin familyConformational statesConformational transitionTissue integrityCell functionCentral mediatorRemarkable convergenceMechanical forcesForce transmissionCytoskeletonMechanotransductionAdhesionFirm adhesionUnanswered questionsIntegrinsNew informationPathwayLigandsThe UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix
Herrera JA, Dingle L, Fernandez M, Venkateswaran RV, Blaikley JF, Lawless C, Schwartz MA. The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix. JCI Insight 2022, 7: e156115. PMID: 35852874, PMCID: PMC9462507, DOI: 10.1172/jci.insight.156115.Peer-Reviewed Original Research