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
2018
Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy
Liao X, Shen Y, Zhang R, Sugi K, Vasudevan NT, Alaiti MA, Sweet DR, Zhou L, Qing Y, Gerson SL, Fu C, Wynshaw-Boris A, Hu R, Schwartz MA, Fujioka H, Richardson B, Cameron MJ, Hayashi H, Stamler JS, Jain MK. Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e4661-e4669. PMID: 29712858, PMCID: PMC5960298, DOI: 10.1073/pnas.1720065115.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiomegalyCardiomyopathiesCells, CulturedHeart FailureKruppel-Like Factor 4Kruppel-Like Transcription FactorsMacrophagesMiceMyocardiumPressureConceptsNonischemic cardiomyopathyKruppel-like factor 4Resident macrophage proliferationNonresident macrophagesHeart failureCardiac functionMyeloid cellsBlood-borne macrophagesPreserves cardiac functionMacrophage proliferationPressure overload hypertrophyValvular diseaseOverload hypertrophyMyocardial angiogenesisAdaptive responseFirst weekMajor causeAngiogenic activityGenetic mutationsMacrophagesFactor 4CardiomyopathyKey transcription factorProliferationDistinct roles
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) signaling
2014
Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling
Baeyens N, Mulligan-Kehoe MJ, Corti F, Simon DD, Ross TD, Rhodes JM, Wang TZ, Mejean CO, Simons M, Humphrey J, Schwartz MA. Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 17308-17313. PMID: 25404299, PMCID: PMC4260558, DOI: 10.1073/pnas.1413725111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisBlotting, WesternCells, CulturedEndothelial CellsFemaleHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalNF-kappa BReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionStress, MechanicalSyndecan-4Vascular Endothelial Growth Factor Receptor-2ConceptsHuman umbilical vein endothelial cellsNF-κBProinflammatory NF-κBAtherosclerotic plaque burdenKruppel-like factor 2Umbilical vein endothelial cellsVEGF receptor 2Appearance of plaquesVein endothelial cellsHypercholesterolemic micePlaque burdenAntiinflammatory pathwayThoracic aortaReceptor 2Endothelial cellsEndothelial alignmentFlow correlatesCausal roleAtherosclerosisFactor 2MiceCyclic stretchLocalization correlatesActivationSyndecan-4