2024
Dysregulated 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-talkMetabolism
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
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 bindingSignalingCellsFibronectinAtherosclerosisArteryAn Osteopontin/CD44 Axis in RhoGDI2-Mediated Metastasis Suppression
Ahmed M, Sottnik JL, Dancik GM, Sahu D, Hansel DE, Theodorescu D, Schwartz MA. An Osteopontin/CD44 Axis in RhoGDI2-Mediated Metastasis Suppression. Cancer Cell 2016, 30: 432-443. PMID: 27593345, PMCID: PMC5154333, DOI: 10.1016/j.ccell.2016.08.002.Peer-Reviewed Original ResearchConceptsBladder cancer metastasisCancer metastasisLymph node metastasisPoor clinical outcomeTumor-associated macrophagesPrimary tumor growthPotential therapeutic targetOsteopontin expression correlatesNode metastasisClinical outcomesPrimary tumorCD44 axisTherapeutic targetTumor aggressivenessMetastasisTumor growthExpression correlatesTumor cellsRac-GEF Tiam1Osteopontin bindsMetastasis suppressionRac1 axisTumorsCD44RhoGDI2
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
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