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
2001
INHIBITION OF INTERFERON-γ–MEDIATED MICROVASCULAR ENDOTHELIAL CELL MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II GENE ACTIVATION BY HMG-COA REDUCTASE INHIBITORS1
Sadeghi M, Tiglio A, Sadigh K, O’Donnell L, Collinge M, Pardi R, Bender J. INHIBITION OF INTERFERON-γ–MEDIATED MICROVASCULAR ENDOTHELIAL CELL MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II GENE ACTIVATION BY HMG-COA REDUCTASE INHIBITORS1. Transplantation 2001, 71: 1262-1268. PMID: 11397960, DOI: 10.1097/00007890-200105150-00014.Peer-Reviewed Original ResearchMeSH KeywordsCholesterolEndothelium, VascularGene Expression RegulationGenes, MHC Class IIHumansHydroxymethylglutaryl-CoA Reductase InhibitorsInterferon-gammaMicrocirculationNuclear ProteinsPromoter Regions, GeneticSimvastatinTrans-ActivatorsTranscriptional ActivationConceptsMicrovascular endothelial cellsClass II transactivatorInhibitory effectVascular diseaseSimvastatin pretreatmentIFN-gammaReductase inhibitorsClass II major histocompatibility complex moleculesCardiac transplant patientsGraft vascular diseaseLate graft failureHMG-CoA reductase inhibitorsHuman leukocyte antigenEffect of simvastatinMajor histocompatibility complex moleculesHLA-DR inductionSTAT-1 phosphorylationCoA reductase inhibitorsHistocompatibility complex moleculesHuman microvascular endothelial cellsInhibition of interferonTranscription-polymerase chain reaction analysisCardiac transplantationTransplant patientsGraft failure
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 SynergismEndothelium, VascularE-SelectinGene 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