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 studies
2022
A mitochondrial contribution to anti-inflammatory shear stress signaling in vascular endothelial cells
Coon BG, Timalsina S, Astone M, Zhuang ZW, Fang J, Han J, Themen J, Chung M, Yang-Klingler YJ, Jain M, Hirschi KK, Yamamato A, Trudeau LE, Santoro M, Schwartz MA. A mitochondrial contribution to anti-inflammatory shear stress signaling in vascular endothelial cells. Journal Of Cell Biology 2022, 221: e202109144. PMID: 35695893, PMCID: PMC9198948, DOI: 10.1083/jcb.202109144.Peer-Reviewed Original ResearchConceptsLaminar shear stressAnti-inflammatory transcription factorHigh laminar shear stressKruppel-like factor 2Vascular endothelial cellsSubsequent mechanistic investigationsArterial lesionsVascular inflammationDisturbed blood flowMyocardial infarctionVascular diseaseVascular remodelingBlood flowKLF2 expressionWhole-genome CRISPREndothelial cellsMajor causeBiomechanical factorsFactor 2Mitochondrial calciumMitochondrial metabolismKLF2InductionMetabolismMitochondrial pathway
2020
Endothelial-to-Mesenchymal Transition, Vascular Inflammation, and Atherosclerosis
Chen PY, Schwartz MA, Simons M. Endothelial-to-Mesenchymal Transition, Vascular Inflammation, and Atherosclerosis. Frontiers In Cardiovascular Medicine 2020, 7: 53. PMID: 32478094, PMCID: PMC7232582, DOI: 10.3389/fcvm.2020.00053.Peer-Reviewed Original ResearchVascular inflammationMesenchymal transitionBiology of atherosclerosisPotential new therapeutic targetChronic progressive diseaseNew therapeutic targetsSelective inflammatory mediatorsProgressive diseaseInflammatory mediatorsAtherosclerotic plaquesBlood flowTherapeutic targetPlaque growthInflammationAtherosclerosisMultiple attemptsDiseaseMolecular mechanismsEndMTPlaques
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 retentionCaveolin-1 Regulates Atherogenesis by Attenuating Low-Density Lipoprotein Transcytosis and Vascular Inflammation Independently of Endothelial Nitric Oxide Synthase Activation
Ramírez CM, Zhang X, Bandyopadhyay C, Rotllan N, Sugiyama MG, Aryal B, Liu X, He S, Kraehling JR, Ulrich V, Lin CS, Velazquez H, Lasunción MA, Li G, Suárez Y, Tellides G, Swirski FK, Lee WL, Schwartz MA, Sessa WC, Fernández-Hernando C. Caveolin-1 Regulates Atherogenesis by Attenuating Low-Density Lipoprotein Transcytosis and Vascular Inflammation Independently of Endothelial Nitric Oxide Synthase Activation. Circulation 2019, 140: 225-239. PMID: 31154825, PMCID: PMC6778687, DOI: 10.1161/circulationaha.118.038571.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseDiet-induced atherosclerosisNO productionVascular inflammationENOS activationEndothelial nitric oxide synthase activationNitric oxide synthase activationAthero-protective functionsLipid metabolic factorsEndothelial cell inflammationNitric oxide synthaseWild-type miceMice Lacking ExpressionProduction of NOExtracellular matrix remodelingInflammatory primingHyperlipidemic miceInflammatory pathwaysAortic archCell inflammationOxide synthaseMetabolic factorsMouse modelAtherosclerosisInflammation
2005
12/15-Lipoxygenase Regulates Intercellular Adhesion Molecule-1 Expression and Monocyte Adhesion to Endothelium Through Activation of RhoA and Nuclear Factor-&kgr;B
Bolick DT, Orr AW, Whetzel A, Srinivasan S, Hatley ME, Schwartz MA, Hedrick CC. 12/15-Lipoxygenase Regulates Intercellular Adhesion Molecule-1 Expression and Monocyte Adhesion to Endothelium Through Activation of RhoA and Nuclear Factor-&kgr;B. Arteriosclerosis Thrombosis And Vascular Biology 2005, 25: 2301-2307. PMID: 16166569, DOI: 10.1161/01.atv.0000186181.19909.a6.Peer-Reviewed Original ResearchMeSH Keywords12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAnimalsAortaArachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseAtherosclerosisCell AdhesionEndothelium, VascularGene ExpressionIntercellular Adhesion Molecule-1MiceMice, Inbred C57BLMice, TransgenicMonocytesNF-kappa BProtein Kinase C-alphaRhoA GTP-Binding ProteinSignal TransductionVasculitisConceptsICAM-1 expressionEndothelial cellsMonocyte adhesionIntercellular adhesion molecule-1 expressionEndothelial ICAM-1 expressionAdhesion molecule-1 expressionNuclear factor-kappaB activationMolecule-1 expressionIntercellular adhesion moleculeNF-kappaB activationRho kinase inhibitor YICAM-1 inductionEndothelial intercellular adhesion moleculeAortic endothelial cellsVascular inflammationC57BL/6J controlsICAM expressionInhibition of RhoATransgenic miceActivation of RhoAHydroxyeicosatetraenoic acidNF-kappaBMRNA expressionNF-kappaB.Nuclear factor