2023
FN (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 ResearchMeSH KeywordsAnimalsAortic Aneurysm, ThoracicFibrillin-1FibronectinsIntegrin alpha5Marfan SyndromeMiceNF-kappa BSwineConceptsContractile 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/
2022
Fibronectin-Integrin α5 Signaling in Vascular Complications of Type 1 Diabetes.
Chen M, Hu R, Cavinato C, Zhuang ZW, Zhang J, Yun S, Fernandez Tussy P, Singh A, Murtada SI, Tanaka K, Liu M, Fernández-Hernando C, Humphrey JD, Schwartz MA. Fibronectin-Integrin α5 Signaling in Vascular Complications of Type 1 Diabetes. Diabetes 2022, 71: 2020-2033. PMID: 35771994, PMCID: PMC9450851, DOI: 10.2337/db21-0958.Peer-Reviewed Original ResearchConceptsVascular complicationsInjection of streptozotocinBlood flow recoveryHigh-fat dietType 1 diabetesInflammatory cell invasionIntegrin α5T1D miceVascular basement membraneVascular diseaseCarotid arteryHindlimb ischemiaMetalloproteinase expressionMain receptorType 1Plaque sizeBeneficial effectsEndothelial cellsMajor causeCell invasionExtracellular matrix proteinsHyperlipidemiaComplicationsBasement membraneT1D
2021
Fibronectin‐Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling
Budatha M, Zhang J, Schwartz MA. Fibronectin‐Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling. Journal Of The American Heart Association 2021, 10: e021160. PMID: 34472370, PMCID: PMC8649308, DOI: 10.1161/jaha.121.021160.Peer-Reviewed Original ResearchConceptsTransverse aortic constrictionPathological vascular remodelingVascular remodelingCarotid ligation modelPartial carotid ligation modelAortic constrictionInflammatory activationEndothelial cellsLigation modelArtery wall hypertrophyTransverse aortic constriction (TAC) modelHigh-fat dietIntegrin α5Aortic constriction modelWild-type miceBasement membranePartial carotid ligationVascular endothelial cellsProvisional matrix proteinsAcute atherosclerosisHyperlipidemic ApoEInflammatory markersLigation surgeryWall hypertrophyAcute model
2018
Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis
Budatha M, Zhang J, Zhuang ZW, Yun S, Dahlman JE, Anderson DG, Schwartz MA. Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis. Journal Of The American Heart Association 2018, 7: e007501. PMID: 29382667, PMCID: PMC5850249, DOI: 10.1161/jaha.117.007501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesAtherosclerosisCyclic Nucleotide Phosphodiesterases, Type 4Disease Models, AnimalExtracellular MatrixFibronectinsFibrosisGenetic Predisposition to DiseaseHindlimbInflammation MediatorsIntegrin alpha2Integrin alpha5IschemiaLeukocytesMaleMatrix MetalloproteinasesMice, Inbred C57BLMice, Knockout, ApoEMuscle, SkeletalNeovascularization, PhysiologicNF-kappa BPhenotypePlaque, AtheroscleroticSignal TransductionVascular RemodelingConceptsEndothelial inflammatory activationAtherosclerotic plaque sizeInflammatory activationPlaque stabilityVascular remodelingEndothelial NF-κB activationSmooth muscle cell contentPlaque sizeFemoral artery ligationMuscle cell contentTreatment of atherosclerosisInflammatory gene expressionPotential therapeutic targetFibrous cap thicknessNF-κB activationSmaller atherosclerotic plaquesArtery ligationAortic rootHindlimb ischemiaCompensatory remodelingAtherosclerotic plaquesTherapeutic targetLeukocyte contentMetalloproteinase expressionEndothelial basement membrane
2016
Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling
Yun S, Budatha M, Dahlman JE, Coon BG, Cameron RT, Langer R, Anderson DG, Baillie G, Schwartz MA. Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling. Nature Cell Biology 2016, 18: 1043-1053. PMID: 27595237, PMCID: PMC5301150, DOI: 10.1038/ncb3405.Peer-Reviewed Original ResearchConceptsInflammatory signalingIntegrin α5Enhanced phosphodiesterase activityExtracellular matrix remodellingModulates inflammationTherapeutic targetInflammationProstacyclin secretionLipid metabolismEndothelial cellsMatrix remodellingVivo knockdownECM remodellingBasement membraneIntegrin α2Phosphodiesterase activityMolecular mechanismsRemodellingΑ5Direct bindingSignalingCellsFibronectinAtherosclerosisArtery