2009
Regional hypoxia correlates with the uptake of a radiolabeled targeted marker of angiogenesis in rat model of myocardial hypertrophy and ischemic injury.
Dobrucki LW, Meoli DF, Hu J, Sadeghi MM, Sinusas AJ. Regional hypoxia correlates with the uptake of a radiolabeled targeted marker of angiogenesis in rat model of myocardial hypertrophy and ischemic injury. Journal Of Physiology And Pharmacology 2009, 60 Suppl 4: 117-23. PMID: 20083860.Peer-Reviewed Original ResearchConceptsMyocardial hypertrophyHypoxic myocardiumMyocardial infarctionRat modelPressure overload-induced myocardial hypertrophyNon-invasive imaging strategyDeficient blood flowDegree of hypoperfusionAbdominal aortic bandingAnterior lateral wallLeft ventricular remodelingIschemic rat modelMarkers of angiogenesisHypoxia-induced angiogenesisPotential clinical useIschemic injuryAortic bandingVentricular remodelingAlphavbeta3 integrin receptorMyocardial hypoxiaImmunohistochemical stainingMyocardial uptakeRodent modelsBlood flowMyocardial segments
2008
Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction
Kalinowski L, Dobrucki LW, Meoli DF, Dione DP, Sadeghi MM, Madri JA, Sinusas AJ. Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction. Journal Of Applied Physiology 2008, 104: 1504-1512. PMID: 18356482, DOI: 10.1152/japplphysiol.00861.2007.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBiomarkersBiotransformationDogsHeterocyclic Compounds, 1-RingHypoxiaImidazolesImmunohistochemistryIntegrin alphaVbeta3IntegrinsMaleMyocardial InfarctionMyocardial IschemiaMyocardiumNeovascularization, PhysiologicOrganometallic CompoundsOrganotechnetium CompoundsRadiopharmaceuticalsRatsRats, Sprague-DawleyTechnetium Tc 99m SestamibiTomography, Emission-Computed, Single-PhotonConceptsMyocardial infarctionInfarct regionCanine studyIschemic heart diseaseCoronary artery occlusionAcute myocardial infarctionMarkers of angiogenesisEx vivo analysisExpression/activationPotential novel targetHypoxia-induced angiogenesisVivo SPECT imagingAlphavbeta3 integrinBRU59-21Artery occlusionNovel noninvasive approachHeart diseaseHistological evidenceMyocardial hypoxiaMyocardial uptakeRP748Rodent studiesAngiogenic therapyInfarctionMyocardial angiogenesis
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 pyrophosphateNoninvasive imaging of myocardial angiogenesis following experimental myocardial infarction
Meoli DF, Sadeghi MM, Krassilnikova S, Bourke BN, Giordano FJ, Dione DP, Su H, Edwards DS, Liu S, Harris TD, Madri JA, Zaret BL, Sinusas AJ. Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. Journal Of Clinical Investigation 2004, 113: 1684-1691. PMID: 15199403, PMCID: PMC420502, DOI: 10.1172/jci20352.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCoronary VesselsDiagnostic ImagingDogsEndothelial CellsEndothelium, VascularHemodynamicsIndium RadioisotopesIntegrin alphaVbeta3MaleMolecular StructureMyocardial InfarctionMyocardiumNeovascularization, PhysiologicQuinolonesRadiopharmaceuticalsRatsRats, Sprague-DawleyTechnetium Tc 99m SestamibiTomography, Emission-Computed, Single-PhotonConceptsMyocardial angiogenesisMyocardial infarctionRadiotracer uptakeInjury-induced angiogenesisChronic rat modelNoninvasive imaging strategiesTherapeutic myocardial angiogenesisExperimental myocardial infarctionFocal radiotracer uptakePotential novel targetSignificant clinical utilityAlphavbeta3 integrinRisk stratificationHistological evidenceHypoperfused regionsRat modelMyocardial radiotracer uptakeClinical utilityNoninvasive evaluationAngiogenic therapyCanine modelInfarct regionInfarctionNovel targetNoninvasive imaging
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