2016
Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; Production
Ceneri N, Zhao L, Young BD, Healy A, Coskun S, Vasavada H, Yarovinsky TO, Ike K, Pardi R, Qin L, Qin L, Tellides G, Hirschi K, Meadows J, Soufer R, Chun HJ, Sadeghi M, Bender JR, Morrison AR. Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; Production. Arteriosclerosis Thrombosis And Vascular Biology 2016, 37: 328-340. PMID: 27834690, PMCID: PMC5269510, DOI: 10.1161/atvbaha.116.308507.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisCells, CulturedCoronary Artery DiseaseCoronary VesselsFemaleGenetic Predisposition to DiseaseHumansInflammation MediatorsInterleukin 1 Receptor Antagonist ProteinInterleukin-1betaMacrophagesMaleMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeuropeptidesPhenotypePlaque, AtheroscleroticPrognosisRac GTP-Binding ProteinsRac1 GTP-Binding ProteinSignal TransductionTransfectionUp-RegulationVascular CalcificationConceptsCoronary calcium burdenIL-1β expressionCalcium burdenSerum IL-1β levelsElevated IL-1βIL-1β levelsCoronary artery diseaseInterleukin-1β expressionCalcified coronary arteryCardiovascular deathCardiovascular eventsArtery diseaseIndependent predictorsClinical outcomesVascular calcificationCoronary arteryIL-1βPlaque calciumAtherosclerotic calcificationExperimental atherogenesisInflammatory regulatorsMacrophage interleukinAtherosclerotic plaquesTherapeutic targetProgressive calcificationThe neuropilin-like protein ESDN regulates insulin signaling and sensitivity
Li X, Jung JJ, Nie L, Razavian M, Zhang J, Samuel V, Sadeghi MM. The neuropilin-like protein ESDN regulates insulin signaling and sensitivity. AJP Heart And Circulatory Physiology 2016, 310: h1184-h1193. PMID: 26921437, PMCID: PMC4867389, DOI: 10.1152/ajpheart.00782.2015.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, CDAorta, ThoracicCell MovementCell ProliferationCells, CulturedDose-Response Relationship, DrugEnzyme ActivationFemaleGenotypeGRB10 Adaptor ProteinInsulinInsulin ResistanceMaleMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein KinasesMuscle, Smooth, VascularMyocytes, Smooth MuscleNeuropilinsPhenotypePhosphorylationProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionTime FactorsUbiquitinationConceptsSignal transductionNovel regulatorSmooth muscle cell-derived neuropilin-like proteinInsulin receptorInsulin receptor signal transductionMitogen-activated protein kinase activationSrc homology 2Novel regulatory mechanismReceptor signal transductionProtein kinase BInsulin signal transductionProtein kinase activationInsulin receptor phosphorylationPleckstrin homologyHomology 2Adaptor proteinTransmembrane proteinGrowth factor receptorKinase activationVascular smooth muscle cell proliferationRegulatory mechanismsKinase BInsulin signalingReceptor phosphorylationNovel therapeutic avenues
2015
Interferon-&ggr;–Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients
Zhou J, Qin L, Yi T, Ali R, Li Q, Jiao Y, Li G, Tobiasova Z, Huang Y, Zhang J, Yun JJ, Sadeghi MM, Giordano FJ, Pober JS, Tellides G. Interferon-&ggr;–Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients. Circulation Research 2015, 117: 943-955. PMID: 26399469, PMCID: PMC4636943, DOI: 10.1161/circresaha.115.306932.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsAortic DiseasesApolipoproteins EAtherosclerosisCardiomyopathiesCardiovascular DiseasesDisease Models, AnimalFemaleGraft RejectionHeart TransplantationHemodynamicsHistocompatibility Antigens Class IIHyperlipidemiasInflammation MediatorsInterferon-gammaLymphocyte ActivationMaleMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutSignal TransductionTh1 CellsVentricular Dysfunction, LeftVentricular Function, LeftConceptsOrgan transplant recipientsCardiovascular diseaseTransplant recipientsEarly-onset cardiovascular diseaseEnd-stage organ failureNative coronary arteriesTh1-type cytokinesT helper cellsHost diseaseAlloimmune responseGraft rejectionAortic stiffeningOrgan failureVentricular dilatationAllogeneic graftsCardiovascular dysfunctionCoronary arteryAortic complianceRisk factorsEffective therapyCardiac contractilityMurine modelAnimal modelsSerological neutralizationImmune system
2014
Calcific Aortic Valve Disease
Yutzey KE, Demer LL, Body SC, Huggins GS, Towler DA, Giachelli CM, Hofmann-Bowman MA, Mortlock DP, Rogers MB, Sadeghi MM, Aikawa E. Calcific Aortic Valve Disease. Arteriosclerosis Thrombosis And Vascular Biology 2014, 34: 2387-2393. PMID: 25189570, PMCID: PMC4199903, DOI: 10.1161/atvbaha.114.302523.Peer-Reviewed Original ResearchConceptsCalcific aortic valve diseaseAortic valve diseaseValve diseaseSurgical valve replacementNational Heart LungNew therapeutic approachesBasic science researchersValve replacementAortic stenosisSignificant morbidityBlood InstituteTherapeutic optionsPatient populationHeart LungTreatment strategiesTherapeutic approachesDisease processOptimal managementFurther studiesAdditional investigationDiagnostic methodsDiseaseGroupMorbidityStenosis
2009
Endothelial and Smooth Muscle-derived Neuropilin-like Protein Regulates Platelet-derived Growth Factor Signaling in Human Vascular Smooth Muscle Cells by Modulating Receptor Ubiquitination*
Guo X, Nie L, Esmailzadeh L, Zhang J, Bender JR, Sadeghi MM. Endothelial and Smooth Muscle-derived Neuropilin-like Protein Regulates Platelet-derived Growth Factor Signaling in Human Vascular Smooth Muscle Cells by Modulating Receptor Ubiquitination*. Journal Of Biological Chemistry 2009, 284: 29376-29382. PMID: 19696027, PMCID: PMC2785569, DOI: 10.1074/jbc.m109.049684.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDown-RegulationHumansMembrane ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Muscle, Smooth, VascularMyocytes, Smooth MusclePhosphorylationPlatelet-Derived Growth FactorProto-Oncogene Proteins c-cblReceptor, Platelet-Derived Growth Factor betaSignal TransductionSrc-Family KinasesUbiquitin-Protein LigasesUbiquitinationConceptsPlatelet-derived growth factorSmooth muscle cell-derived neuropilin-like proteinPDGF receptorPlatelet-derived growth factor signalingPrototypic growth factorsE3 ubiquitin ligaseGrowth factor signalingExpression levelsPrimary human VSMCsHuman vascular smooth muscle cellsVascular smooth muscle cell growthReceptor ubiquitinationGrowth factorUbiquitin ligaseFactor signalingRNA interferenceC-CblVascular smooth muscle cellsSmooth muscle cell growthMuscle cell growthVSMC DNA synthesisUbiquitinationESDNHuman VSMCsSmooth muscle cells
2006
HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced “inside-out” signaling to extracellular matrix by preventing RhoA activation
Xu H, Zeng L, Peng H, Chen S, Jones J, Chew TL, Sadeghi MM, Kanwar YS, Danesh FR. HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced “inside-out” signaling to extracellular matrix by preventing RhoA activation. American Journal Of Physiology. Renal Physiology 2006, 291: f995-f1004. PMID: 16774905, DOI: 10.1152/ajprenal.00092.2006.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsAnimalsCells, CulturedCollagen Type IVExtracellular MatrixFocal Adhesion Protein-Tyrosine KinasesHydroxymethylglutaryl-CoA Reductase InhibitorsIntegrin beta1Mesangial CellsMevalonic AcidPhosphorylationProlineRatsRhoA GTP-Binding ProteinSignal TransductionSimvastatinTritiumTyrosineVascular Endothelial Growth Factor AConceptsRhoA activationIntact actin cytoskeletonCell signaling cascadesPrecise signaling mechanismUnderlying molecular mechanismsActin cytoskeletonECM expansionMevalonate depletionSignaling cascadesIntegrin activationMevalonate pathwayECM accumulationMolecular mechanismsVEGF stimulationSignaling mechanismComplex biologyExtracellular matrixPleiotropic effectsAngiogenic polypeptideType IV collagen accumulationEndothelial cell permeabilityExtracellular matrix accumulationCell permeabilityGrowth factorPathological processes
2005
HMG CoA reductase inhibition modulates VEGF‐induced endothelial cell hyperpermeability by preventing RhoA activation and myosin regulatory light chain phosphorylation
Zeng L, Xu H, Chew T, Eng E, Sadeghi MM, Adler S, Kanwar YS, Danesh FR. HMG CoA reductase inhibition modulates VEGF‐induced endothelial cell hyperpermeability by preventing RhoA activation and myosin regulatory light chain phosphorylation. The FASEB Journal 2005, 19: 1845-1847. PMID: 16160062, DOI: 10.1096/fj.05-4240fje.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBlotting, WesternCell LineCytoplasmCytoskeletonCytosolDiabetic NephropathiesElectric ImpedanceEndothelial CellsEndothelium, VascularGreen Fluorescent ProteinsHydroxymethylglutaryl CoA ReductasesHydroxymethylglutaryl-CoA Reductase InhibitorsKidney GlomerulusMevalonic AcidMicroscopy, ConfocalModels, BiologicalModels, StatisticalMyosin Light ChainsPermeabilityPhosphorylationRatsRhoA GTP-Binding ProteinSignal TransductionSimvastatinTransfectionVascular Endothelial Growth Factor A
2004
Simvastatin Modulates Angiotensin II Signaling Pathway by Preventing Rac1-Mediated Upregulation of p27
ZENG L, XU H, CHEW TL, CHISHOLM R, SADEGHI MM, KANWAR YS, DANESH FR. Simvastatin Modulates Angiotensin II Signaling Pathway by Preventing Rac1-Mediated Upregulation of p27. Journal Of The American Society Of Nephrology 2004, 15: 1711-1720. PMID: 15213258, DOI: 10.1097/01.asn.0000129839.91567.68.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAngiotensin IIAnimalsBlotting, WesternCell Cycle ProteinsCell LineCyclin-Dependent Kinase Inhibitor p27Hydrogen PeroxideHydroxymethylglutaryl-CoA Reductase InhibitorsLeucineMicroscopy, ConfocalModels, BiologicalOxidation-ReductionPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRac1 GTP-Binding ProteinRatsSignal TransductionSimvastatinTransfectionTumor Suppressor ProteinsUp-RegulationConceptsP27 protein expressionAng IIAng II stimulationIntracellular H2O2 productionModulatory effectsMesangial cellsProtein expressionII stimulationCyclin-dependent kinase inhibitor p27P27 proteinEffect of simvastatinCell cycle levelSmall GTPAkt kinaseH2O2 productionRat mesangial cellsCholesterol-lowering propertiesAddition of mevalonateLipid attachmentDownstream activationRac1 activitySignaling pathwaysAkt activationIsoprenoid intermediatesGeranylgeranyl pyrophosphate
2002
3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced proliferation of mesangial cells via modulation of Rho GTPase/ p21 signaling pathway: Implications for diabetic nephropathy
Danesh FR, Sadeghi MM, Amro N, Philips C, Zeng L, Lin S, Sahai A, Kanwar YS. 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced proliferation of mesangial cells via modulation of Rho GTPase/ p21 signaling pathway: Implications for diabetic nephropathy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 8301-8305. PMID: 12048257, PMCID: PMC123062, DOI: 10.1073/pnas.122228799.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell MembraneCells, CulturedCyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsDiabetic NephropathiesDNA ReplicationEnzyme InhibitorsGlomerular MesangiumGlucoseHydroxymethylglutaryl-CoA Reductase InhibitorsModels, BiologicalProtein PrenylationProtein TransportRatsRho GTP-Binding ProteinsSignal TransductionSimvastatinTransfectionConceptsDiabetic nephropathyMesangial cellsP21 protein expressionProtein expressionCdk2 kinase activityReductase inhibitorsExposure of MCsHigh glucose-induced proliferationProliferation of MCsUse of statinsHMG-CoA reductase inhibitorsLipid-lowering agentsCoronary heart diseaseCholesterol-lowering effectCoA reductase inhibitorsGlucose-induced proliferationGlomerular mesangial cellsRat mesangial cellsCholesterol-lowering propertiesStatin therapyHeart diseaseClinical dataCell cycle levelMC proliferationHigh glucose
2000
Simvastatin Modulates Cytokine-Mediated Endothelial Cell Adhesion Molecule Induction: Involvement of an Inhibitory G Protein
Sadeghi M, Collinge M, Pardi R, Bender J. Simvastatin Modulates Cytokine-Mediated Endothelial Cell Adhesion Molecule Induction: Involvement of an Inhibitory G Protein. The Journal Of Immunology 2000, 165: 2712-2718. PMID: 10946302, DOI: 10.4049/jimmunol.165.5.2712.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicBiological TransportCell Adhesion MoleculesCells, CulturedCholesterolCytokinesDrug SynergismE-SelectinEndothelium, VascularGene Expression RegulationGTP-Binding Protein alpha Subunits, Gi-GoHumansHydroxymethylglutaryl-CoA Reductase InhibitorsIntercellular Adhesion Molecule-1Interleukin-1NF-kappa BRNA, MessengerSignal TransductionSimvastatinSodium FluorideUmbilical VeinsVascular Cell Adhesion Molecule-1ConceptsEffect of simvastatinCytokine-induced expressionIL-1Endothelial CAMsEndothelial cell adhesion molecules E-selectinNF-kappaBProinflammatory cytokines IL-1Cell adhesion molecules E-selectinAdhesion molecules E-selectinPotent immune modulatorG protein activator NaFCytokines IL-1G protein-coupled pathwayInhibitory G proteinCytokine-mediated activationSelectin mRNA levelsBasal toneProinflammatory cytokinesGialpha proteinsImmune modulatorsTNF-alphaICAM-1Pertussis toxinE-selectinEndothelial response