2019
Angiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure
Pfau D, Thorn SL, Zhang J, Mikush N, Renaud JM, Klein R, deKemp RA, Wu X, Hu X, Sinusas AJ, Young LH, Tirziu D. Angiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure. Scientific Reports 2019, 9: 5791. PMID: 30962467, PMCID: PMC6453892, DOI: 10.1038/s41598-019-42113-0.Peer-Reviewed Original ResearchMeSH KeywordsAminobutyratesAngiotensin Receptor AntagonistsAnimalsBiphenyl CompoundsDrug CombinationsHeartHeart FailureMaleMyocardial Reperfusion InjuryMyocardiumNeovascularization, PhysiologicNeprilysinOrganotechnetium CompoundsPeptides, CyclicRatsRats, Inbred LewSingle Photon Emission Computed Tomography Computed TomographyTetrazolesValsartanVascular Endothelial Growth Factor AVentricular RemodelingConceptsSacubitril/valsartanExperimental heart failureHeart failureMyocardial infarctionMyocardial remodelingAngiotensin receptor neprilysin inhibitorAngiotensin receptor blocker valsartanMicroSPECT/CT imagingReceptor blocker valsartanHeart failure patientsProgressive LV dilationGlobal LV functionLV contractile dysfunctionNeprilysin inhibitor sacubitrilBorder zoneLimited remodelingFailure patientsInhibitor therapyMale LewisWeeks treatmentLV dilationLV functionNeprilysin inhibitorContractile dysfunctionInterstitial fibrosis
2013
Multimodality Imaging Approach for Serial Assessment of Regional Changes in Lower Extremity Arteriogenesis and Tissue Perfusion in a Porcine Model of Peripheral Arterial Disease
Stacy MR, Yu da Y, Maxfield MW, Jaba IM, Jozwik BP, Zhuang ZW, Lin BA, Hawley CL, Caracciolo CM, Pal P, Tirziu D, Sampath S, Sinusas AJ. Multimodality Imaging Approach for Serial Assessment of Regional Changes in Lower Extremity Arteriogenesis and Tissue Perfusion in a Porcine Model of Peripheral Arterial Disease. Circulation Cardiovascular Imaging 2013, 7: 92-99. PMID: 24170237, PMCID: PMC3929970, DOI: 10.1161/circimaging.113.000884.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriesCapillariesCollateral CirculationDisease Models, AnimalLower ExtremityMaleMultimodal ImagingNeovascularization, PhysiologicPerfusion ImagingPeripheral Arterial DiseasePredictive Value of TestsRegional Blood FlowReproducibility of ResultsSwineTomography, Emission-Computed, Single-PhotonTomography, X-Ray ComputedConceptsPeripheral arterial diseaseSPECT/CT imagingArterial diseaseWeeks postocclusionProximal musclesCT imagingCapillary densityTissue perfusionPorcine modelLower extremity perfusionSingle photon emission tomographyFemoral artery occlusionMultimodality Imaging ApproachPhoton emission tomographyGamma countingIschemic calfNonischemic hindlimbsExtremity perfusionArtery occlusionLimb ischemiaMuscle perfusionSerial assessmentSerial changesCT angiographySPECT perfusionNO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth
Jaba IM, Zhuang ZW, Li N, Jiang Y, Martin KA, Sinusas AJ, Papademetris X, Simons M, Sessa WC, Young LH, Tirziu D. NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth. Journal Of Clinical Investigation 2013, 123: 1718-1731. PMID: 23454748, PMCID: PMC3613910, DOI: 10.1172/jci65112.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, BiologicalAnimalsCell EnlargementCells, CulturedCoronary VesselsEndothelium, VascularHeart VentriclesMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, TransgenicMultiprotein ComplexesMyocytes, CardiacNeovascularization, PhysiologicNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthasePlacenta Growth FactorPregnancy ProteinsProteinsProteolysisProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyRGS ProteinsSignal TransductionTOR Serine-Threonine KinasesConceptsCardiomyocyte growthAkt/mTORC1 signalingNovel NO-dependent mechanismProteasomal degradationCoordination of angiogenesisMTORC1 signalingConditional overexpressionMurine cardiac tissueG proteinsTransgenic expressionAkt/Physiological mechanismsMyocyte growthVessel growthGrowth factorTransgenic miceHypertrophic responseAngiogenesisKnockout miceMyocardial hypertrophyExpressionGrowthCardiac hypertrophyNOS inhibitor L-NAMEInduction
2012
Endothelial Nuclear Factor-&kgr;B–Dependent Regulation of Arteriogenesis and Branching
Tirziu D, Jaba IM, Yu P, Larrivée B, Coon BG, Cristofaro B, Zhuang ZW, Lanahan AA, Schwartz MA, Eichmann A, Simons M. Endothelial Nuclear Factor-&kgr;B–Dependent Regulation of Arteriogenesis and Branching. Circulation 2012, 126: 2589-2600. PMID: 23091063, PMCID: PMC3514045, DOI: 10.1161/circulationaha.112.119321.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBecaplerminBrainDisease Models, AnimalEndothelial CellsHindlimbHuman Umbilical Vein Endothelial CellsHumansHypoxia-Inducible Factor 1, alpha SubunitIschemiaMiceMice, TransgenicNeovascularization, PathologicNeovascularization, PhysiologicNF-kappa B p50 SubunitProto-Oncogene Proteins c-sisRetinaVascular Endothelial Growth Factor AConceptsNuclear factor-κB activationCollateral formationReduced adhesion molecule expressionHypoxia-inducible factor-1α levelsDistal tissue perfusionVascular endothelial growth factorAdhesion molecule expressionPlatelet-derived growth factor-BBEndothelial growth factorGrowth factor-BBMolecule expressionMonocyte influxCollateral networkTissue perfusionImmature vesselsArterial networkBaseline levelsNFκB activationNuclear factorFactor-BBGrowth factor
2010
Cell Communications in the Heart
Tirziu D, Giordano FJ, Simons M. Cell Communications in the Heart. Circulation 2010, 122: 928-937. PMID: 20805439, PMCID: PMC2941440, DOI: 10.1161/circulationaha.108.847731.Peer-Reviewed Original ResearchAnimalsCardiomegalyCell CommunicationEndothelium, VascularHeartHumansMyocardiumNeovascularization, PhysiologicSignal Transduction
2008
Endothelium as master regulator of organ development and growth
Tirziu D, Simons M. Endothelium as master regulator of organ development and growth. Vascular Pharmacology 2008, 50: 1-7. PMID: 18804188, PMCID: PMC2630387, DOI: 10.1016/j.vph.2008.08.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationEmbryonic DevelopmentEndothelium, VascularGene Expression Regulation, DevelopmentalHumansNeovascularization, PhysiologicOrganogenesisParacrine CommunicationSignal Transduction
2007
Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice
Tirziu D, Chorianopoulos E, Moodie KL, Palac RT, Zhuang ZW, Tjwa M, Roncal C, Eriksson U, Fu Q, Elfenbein A, Hall AE, Carmeliet P, Moons L, Simons M. Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice. Journal Of Clinical Investigation 2007, 117: 3188-3197. PMID: 17975666, PMCID: PMC2045601, DOI: 10.1172/jci32024.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenic ProteinsAnimalsCardiomegalyCells, CulturedEchocardiographyEndothelial CellsEnzyme InhibitorsHeartHemodynamicsMiceMice, Inbred C57BLMice, TransgenicMyocardiumMyocytes, CardiacNeovascularization, PhysiologicNG-Nitroarginine Methyl EsterOrgan SizeRatsRats, Sprague-DawleyTransgenesConceptsMyocardial hypertrophyHeart sizeNormal heart sizeENOS inhibitor L-NAMEInhibitor L-NAMEAtrial natriuretic factorHypertrophic marker expressionNormal adult mouse heartAdult mouse heartAngiogenic growth factorsL-NAMEBeta-MHCCardiac massMyocardial infarctionMyocardial functionNatriuretic factorCardiac performanceCardiomyocyte sizeTransgenic miceStimulation periodHeart growthHypertrophy markersMarker expressionMouse heartsMurine heart
2005
Angiogenesis in the human heart: Gene and cell therapy
Tirziu D, Simons M. Angiogenesis in the human heart: Gene and cell therapy. Angiogenesis 2005, 8: 241-251. PMID: 16308736, DOI: 10.1007/s10456-005-9011-z.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis Inducing AgentsCell TransplantationCoronary VesselsGenetic TherapyHumansMyocardial IschemiaNeovascularization, PhysiologicStem CellsConceptsNew vessel growthCell therapyPeripheral arterial diseaseVessel growthBest cell typeStimulation of angiogenesisMechanism of actionArterial diseasePatient selectionClinical trialsBlood supplyIschemic tissueIschemic diseasesNew therapiesTherapyGrowth factorHuman heartDiseaseCell typesAngiogenesisMain biological processesPatientsMultiple questionsTrialsAdenoviral PR39 improves blood flow and myocardial function in a pig model of chronic myocardial ischemia by enhancing collateral formation
Post MJ, Sato K, Murakami M, Bao J, Tirziu D, Pearlman JD, Simons M. Adenoviral PR39 improves blood flow and myocardial function in a pig model of chronic myocardial ischemia by enhancing collateral formation. AJP Regulatory Integrative And Comparative Physiology 2005, 290: r494-r500. PMID: 16254127, DOI: 10.1152/ajpregu.00460.2005.Peer-Reviewed Original ResearchConceptsChronic myocardial ischemiaCollateral formationMyocardial ischemiaBlood flowPig modelAdvanced coronary artery diseaseGrowth factorCoronary artery diseaseHypoxia-inducible factor-1alphaRegional blood flowUpregulation of VEGFDose-dependent mannerFGF receptor expressionArtery diseaseCollateral scoreIschemic myocardiumIndividual growth factorsMyocardial functionReceptor expressionReal-time PCRRegional perfusionLocal VEGFPeptide injectionAngiogenic therapyRegional functionDelayed Arteriogenesis in Hypercholesterolemic Mice
Tirziu D, Moodie KL, Zhuang ZW, Singer K, Helisch A, Dunn JF, Li W, Singh J, Simons M. Delayed Arteriogenesis in Hypercholesterolemic Mice. Circulation 2005, 112: 2501-2509. PMID: 16230502, DOI: 10.1161/circulationaha.105.542829.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoprotein B-48Apolipoproteins BBlood Flow VelocityDisease Models, AnimalEndothelium, VascularFemoral ArteryHumansIn Vitro TechniquesIschemiaMagnetic Resonance ImagingMiceMice, KnockoutNeovascularization, PhysiologicOligonucleotide Array Sequence AnalysisReceptors, LDLUmbilical VeinsConceptsFemoral artery ligationControl miceLaser Doppler imagingArtery ligationTissue perfusionDay 7Doppler imagingReceptor 1Strain-matched control miceVascular cell adhesion molecule-1Monocyte/macrophage influxCell adhesion molecule-1Hypercholesterolemic low-density lipoproteinDistal limb perfusionMacrophage scavenger receptor 1Growth factor therapyIschemia-induced angiogenesisRestoration of perfusionAdhesion molecule-1Arterial blood flowHypoxia-inducible factor-1alphaLow-density lipoproteinScavenger receptor 1Controls 3 daysFactor therapy