2024
Platelet Mitochondrial Fusion and Function in Vascular Integrity
Tyagi T, Yarovinsky T, Faustino E, Hwa J. Platelet Mitochondrial Fusion and Function in Vascular Integrity. Circulation Research 2024, 134: 162-164. PMID: 38236952, PMCID: PMC10798220, DOI: 10.1161/circresaha.123.323867.Peer-Reviewed Original Research
2023
Immune Modulation of Innate and Adaptive Responses Restores Immune Surveillance and Establishes Antitumor Immunologic Memory.
Alvero A, Fox A, Madina B, Krady M, Gogoi R, Chehade H, Nakaar V, Almassian B, Yarovinsky T, Rutherford T, Mor G. Immune Modulation of Innate and Adaptive Responses Restores Immune Surveillance and Establishes Antitumor Immunologic Memory. Cancer Immunology Research 2023, 12: 261-274. PMID: 38078853, PMCID: PMC11027955, DOI: 10.1158/2326-6066.cir-23-0127.Peer-Reviewed Original ResearchPD-L1Immunological memoryImmune surveillanceLong-term anti-tumor effectsAnti-tumor immunological memoryAnti-tumor immune responseImmune modulatory capacityAnti-tumor responseOvarian cancer patientsAnti-tumoral responseAnti-tumor effectsImmune regulatory genesSelf-amplifying RNAVirus-like vesiclesPotent CD8MDSC expansionAdaptive armsCurrent immunotherapiesOncolytic capacityPrevent recurrenceAntitumor cytokinesCancer patientsImmune modulationImmune modulatorsOncolytic effectGuidelines on the use of sex and gender in cardiovascular research
Usselman C, Lindsey M, Robinson A, Habecker B, Taylor C, Merryman W, Kimmerly D, Bender J, Regensteiner J, Moreau K, Pilote L, Wenner M, O'Brien M, Yarovinsky T, Stachenfeld N, Charkoudian N, Denfeld Q, Moreira-Bouchard J, Pyle W, DeLeon-Pennell K. Guidelines on the use of sex and gender in cardiovascular research. AJP Heart And Circulatory Physiology 2023, 326: h238-h255. PMID: 37999647, PMCID: PMC11219057, DOI: 10.1152/ajpheart.00535.2023.Peer-Reviewed Original ResearchFishing for “complements” with vascular organoid models of microvascular disease
Gu S, Yarovinsky T, Hwa J. Fishing for “complements” with vascular organoid models of microvascular disease. Cell Stem Cell 2023, 30: 1285-1286. PMID: 37802032, DOI: 10.1016/j.stem.2023.09.004.Peer-Reviewed Original ResearchDistinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages
Wilcox N, Yarovinsky T, Pandya P, Ramgolam V, Moro A, Wu Y, Nicoli S, Hirschi K, Bender J. Distinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages. IScience 2023, 26: 107985. PMID: 38047075, PMCID: PMC10690575, DOI: 10.1016/j.isci.2023.107985.Peer-Reviewed Original ResearchBone marrow-derived macrophagesTranslation rateAffinity purification assaysGene expression programsTissue-resident macrophagesExpression programsTranscriptional signalsTranslational profilesTranscriptome analysisPosttranscriptional regulationMRNA translationRNA-seqMarrow-derived macrophagesPurification assaysRNA expression levelsProtein HuR.MRNA stabilityDistinct hypoxiaEmbryonic originPotential therapeutic targetTranscriptsExpression levelsAcute perturbationTherapeutic targetIschemic myocardiumCancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence
Chen J, Madina B, Ahmadi E, Yarovinsky T, Krady M, Meehan E, Wang I, Ye X, Pitmon E, Ma X, Almassian B, Nakaar V, Wang K. Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence. Acta Pharmaceutica Sinica B 2023, 14: 335-349. PMID: 38261838, PMCID: PMC10792965, DOI: 10.1016/j.apsb.2023.08.034.Peer-Reviewed Original ResearchCancer immunotherapyTumor recurrenceShort hairpin RNASurvival benefitIL-12Immune mechanismsLong-term survival benefitIL-17 receptor ACancer-promoting inflammationLarge established tumorsMultiple immune mechanismsPD-L1 pathwayT cell exhaustionDeath ligand 1Human cancer immunotherapySelf-amplifying mRNATumor-bearing miceVirus-like vesiclesMechanism of protectionCombined immunomodulationContralateral tumorsIL-17Established tumorsAbscopal effectImmunological memoryImmune modulation of innate and adaptive responses by CARG-2020 restore immunosurveillance and establish anti-tumoral immunological memory (049)
Alvero A, Fox A, Madina B, Krady M, Gogoi R, Yarovinsky T, Nakaar V, Almassian B, Mor G. Immune modulation of innate and adaptive responses by CARG-2020 restore immunosurveillance and establish anti-tumoral immunological memory (049). Gynecologic Oncology 2023, 176: s42. DOI: 10.1016/j.ygyno.2023.06.522.Peer-Reviewed Original ResearchPyroptosis in cardiovascular diseases: Pumping gasdermin on the fire
Yarovinsky T, Su M, Chen C, Xiang Y, Tang W, Hwa J. Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire. Seminars In Immunology 2023, 69: 101809. PMID: 37478801, PMCID: PMC10528349, DOI: 10.1016/j.smim.2023.101809.Peer-Reviewed Original ResearchConceptsPost-translational modificationsAcute cardiovascular eventsChronic cardiovascular diseaseCardiovascular diseaseSmall molecule inhibitorsPyroptosis resultsGenetic toolsGasdermin proteinsWhole organismInflammatory caspasesCardiovascular eventsCell deathMolecule inhibitorsCell typesProteolytic cleavageCellular mechanismsActivation of inflammasomesCardiovascular systemKnockout animalsAmplification of inflammationRole of pyroptosisPro-inflammatory processesDifferent cellsNovel therapeutic approachesPyroptosis
2022
Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells
Tyagi T, Jain K, Yarovinsky TO, Chiorazzi M, Du J, Castro C, Griffin J, Korde A, Martin KA, Takyar SS, Flavell RA, Patel AA, Hwa J. Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells. Journal Of Experimental Medicine 2022, 220: e20212218. PMID: 36305874, PMCID: PMC9814191, DOI: 10.1084/jem.20212218.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsTLT-1Non-small cell lung cancer patientsCell lung cancer patientsTREM-like transcript-1Tumor immunosuppressive mechanismsT cell suppressionLung cancer patientsPatient T cellsNF-κB pathwayPatient-derived tumorsDistinct activation phenotypesNSCLC patientsImmunosuppressive mechanismsSyngeneic tumorsHumanized miceImmunoregulatory rolePrognostic significanceImmunocompetent miceCancer patientsCell suppressionActivation phenotypeReduced tumorTumor growth
2020
Reduced Platelet miR-223 Induction in Kawasaki Disease Leads to Severe Coronary Artery Pathology Through a miR-223/PDGFRβ Vascular Smooth Muscle Cell Axis
Zhang Y, Wang Y, Zhang L, Xia L, Zheng M, Zeng Z, Liu Y, Yarovinsky T, Ostriker AC, Fan X, Weng K, Su M, Huang P, Martin KA, Hwa J, Tang WH. Reduced Platelet miR-223 Induction in Kawasaki Disease Leads to Severe Coronary Artery Pathology Through a miR-223/PDGFRβ Vascular Smooth Muscle Cell Axis. Circulation Research 2020, 127: 855-873. PMID: 32597702, PMCID: PMC7486265, DOI: 10.1161/circresaha.120.316951.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAnimalsBlood PlateletsCase-Control StudiesCells, CulturedChildChild, PreschoolCoronary Artery DiseaseCoronary VesselsDisease Models, AnimalFemaleHumansInfantMaleMice, Inbred C57BLMice, KnockoutMicroRNAsMucocutaneous Lymph Node SyndromeMuscle, Smooth, VascularMyocytes, Smooth MusclePlatelet ActivationProspective StudiesReceptor, Platelet-Derived Growth Factor betaSeverity of Illness IndexSignal TransductionYoung AdultConceptsSevere coronary pathologyCoronary artery pathologyKawasaki diseaseCoronary pathologyArtery pathologyMiR-223Medial damageHealthy controlsVSMC dedifferentiationHallmark of KDMiR-223 knockout miceVascular smooth muscle cell dedifferentiationSmooth muscle cell dedifferentiationPlatelet miR-223Platelet-derived miRNAsVSMC differentiationMedial elastic fibersMiR-223 levelsMuscle cell dedifferentiationPotential therapeutic strategyInhibitor imatinib mesylateVascular smooth muscle cell phenotypeSmooth muscle cell phenotypeMiR-223 mimicsUptake of platelets
2019
Virus-like Vesicles Expressing Multiple Antigens for Immunotherapy of Chronic Hepatitis B
Yarovinsky TO, Mason SW, Menon M, Krady MM, Haslip M, Madina BR, Ma X, Moshkani S, Chiale C, Pal AC, Almassian B, Rose JK, Robek MD, Nakaar V. Virus-like Vesicles Expressing Multiple Antigens for Immunotherapy of Chronic Hepatitis B. IScience 2019, 21: 391-402. PMID: 31704650, PMCID: PMC6889364, DOI: 10.1016/j.isci.2019.10.040.Peer-Reviewed Original ResearchHepatitis B virusChronic hepatitis BHepatitis BSerum HBV surface antigenVirus-like vesiclesLiver HBV RNAPersistent HBV replicationHBV surface antigenImmune exhaustionChronic hepatitisHBV antigensHBV infectionBooster immunizationCD8 TChronic modelHBV replicationImmunotherapeutic approachesLiver injuryNaive miceHBV RNAB virusCurrent treatmentSurface antigenUnmet needMultiple antigensAndrogens drive microvascular endothelial dysfunction in women with polycystic ovary syndrome: role of the endothelin B receptor
Usselman CW, Yarovinsky T, Steele FE, Leone CA, Taylor HS, Bender JR, Stachenfeld NS. Androgens drive microvascular endothelial dysfunction in women with polycystic ovary syndrome: role of the endothelin B receptor. The Journal Of Physiology 2019, 597: 2853-2865. PMID: 30847930, DOI: 10.1113/jp277756.Peer-Reviewed Original ResearchMeSH KeywordsAdultAndrogensCardiovascular DiseasesDihydrotestosteroneEndothelin-1Endothelium, VascularEstrogensEthinyl EstradiolFemaleGlucose Tolerance TestHumansMicrovesselsNitric OxideObesityPolycystic Ovary SyndromeReceptor, Endothelin BSkinVascular Endothelial Growth Factor AVasodilationYoung AdultConceptsPolycystic ovary syndromeCardiovascular dysfunctionEndothelial dysfunctionOvary syndromeEndothelin-1Endothelial functionNO productionAndrogen receptor-dependent mannerEndothelin-B receptor subtypeCardiovascular risk factorsMicrovascular endothelial dysfunctionMicrovascular endothelial functionCutaneous vascular conductanceB receptor subtypesEndothelin B receptorLaser Doppler flowmetryNitric oxide inhibitionReceptor-dependent mannerEndothelial cell NO productionDose-response curveVasodilating responsePCOS subjectsLean womenObese womenVascular conductance
2018
T cell LFA-1-induced proinflammatory mRNA stabilization is mediated by the p38 pathway kinase MK2 in a process regulated by hnRNPs C, H1 and K
Rao GK, Wong A, Collinge M, Sarhan J, Yarovinsky TO, Ramgolam VS, Gaestel M, Pardi R, Bender JR. T cell LFA-1-induced proinflammatory mRNA stabilization is mediated by the p38 pathway kinase MK2 in a process regulated by hnRNPs C, H1 and K. PLOS ONE 2018, 13: e0201103. PMID: 30048492, PMCID: PMC6065199, DOI: 10.1371/journal.pone.0201103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Culture TechniquesCytoplasmELAV-Like Protein 1Heterogeneous-Nuclear RibonucleoproteinsHumansIntracellular Signaling Peptides and ProteinsJurkat CellsLymphocyte Function-Associated Antigen-1Mice, Inbred C57BLMice, KnockoutProtein Serine-Threonine KinasesProteomeRNA StabilityRNA, MessengerSignal TransductionT-LymphocytesConceptsKinase MK2Β2-integrin lymphocyte function-associated antigen-1AU-rich elementsLymphocyte function-associated antigen-1Integrin lymphocyte function-associated antigen-1HuR localizationProtein HuR.Key regulatorMRNA stabilizationCritical activatorCytoplasmic translocationHuR activitySequential activationHuRIntricate processFunction-associated antigen-1MRNAEngagement resultsMK2Antigen 1H1ActivationHnRNPsHuR.Transcripts
2014
Chemokine-coupled β2 integrin–induced macrophage Rac2–Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis
Morrison AR, Yarovinsky TO, Young BD, Moraes F, Ross TD, Ceneri N, Zhang J, Zhuang ZW, Sinusas AJ, Pardi R, Schwartz MA, Simons M, Bender JR. Chemokine-coupled β2 integrin–induced macrophage Rac2–Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis. Journal Of Experimental Medicine 2014, 211: 1957-1968. PMID: 25180062, PMCID: PMC4172219, DOI: 10.1084/jem.20132130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriesCD18 AntigensDNA PrimersFlow CytometryHumansMiceMice, Inbred C57BLMonocytesNeovascularization, PhysiologicNonmuscle Myosin Type IIARac GTP-Binding ProteinsReal-Time Polymerase Chain ReactionReceptors, CCR2RNA StabilityVascular Endothelial Growth Factor AX-Ray MicrotomographyConceptsMyosin IIASignal transduction eventsHuR translocationRapid nuclearTransduction eventsProteomic analysisProtein HuR.Induction of arteriogenesisMRNA stabilityMRNA stabilizationNovel roleCytosolic translocationMyosin-9ICAM-1 adhesionReceptor engagementDevelopmental vasculogenesisCellular effectorsMolecular triggersTranslocationHeavy chainGrowth factorMyeloid cellsVascular endothelial growth factorKey molecular triggerCCL2 stimulationCeramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis
Mehra VC, Jackson E, Zhang XM, Jiang XC, Dobrucki LW, Yu J, Bernatchez P, Sinusas AJ, Shulman GI, Sessa WC, Yarovinsky TO, Bender JR. Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis. American Journal Of Pathology 2014, 184: 1562-1576. PMID: 24606881, PMCID: PMC4005977, DOI: 10.1016/j.ajpath.2014.01.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaArteriesCattleCeramidesDiet, High-FatEndothelial CellsEnzyme ActivationExtracellular Signal-Regulated MAP KinasesHaploinsufficiencyHindlimbHumansIschemiaMice, Inbred C57BLNeovascularization, PhysiologicNitric OxideNitric Oxide Synthase Type IIIPalmitic AcidPhosphorylationProtein Phosphatase 2Proto-Oncogene Proteins c-aktSerine C-PalmitoyltransferaseSignal TransductionVascular Endothelial Growth Factor AConceptsPP2A inhibitor okadaic acidProtein phosphatase 2AInhibitor okadaic acidVEGF-induced signalingSerine palmitoyltransferase inhibitor myriocinDe novo ceramide synthesisPhosphatase 2AENOS agonistsNovo ceramide synthesisPalmitic acidAngiogenic responsePotential molecular targetsOkadaic acidEndothelial cellsEarly speciesEndothelial cell responsesCord formationVEGFR2 phosphorylationSaturated free fatty acidVEGF resistanceCeramide synthesisResistance mechanismsMolecular targetsVascular homeostasisPhosphorylation
2012
Role of phospholipid scramblase 1 in type I interferon-induced protection from staphylococcal α-toxin
Yarovinsky TO. Role of phospholipid scramblase 1 in type I interferon-induced protection from staphylococcal α-toxin. Virulence 2012, 3: 457-458. PMID: 23076241, PMCID: PMC3485986, DOI: 10.4161/viru.21329.Commentaries, Editorials and LettersVirus-cell fusion as a trigger of innate immunity dependent on the adaptor STING
Holm CK, Jensen SB, Jakobsen MR, Cheshenko N, Horan KA, Moeller HB, Gonzalez-Dosal R, Rasmussen SB, Christensen MH, Yarovinsky TO, Rixon FJ, Herold BC, Fitzgerald KA, Paludan SR. Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. Nature Immunology 2012, 13: 737-743. PMID: 22706339, PMCID: PMC3411909, DOI: 10.1038/ni.2350.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell FusionChemokine CXCL10HEK293 CellsHeLa CellsHerpesvirus 1, HumanHumansImmunity, InnateInterferon Type ILeukocytesLymphocyte ActivationMacrophagesMembrane FusionMembrane GlycoproteinsMembrane ProteinsMiceMice, KnockoutMyeloid Differentiation Factor 88Signal TransductionToll-Like Receptor 7Toll-Like Receptor 9Virus InternalizationMacrophage β2 Integrin–Mediated, HuR-Dependent Stabilization of Angiogenic Factor–Encoding mRNAs in Inflammatory Angiogenesis
Zhang J, Modi Y, Yarovinsky T, Yu J, Collinge M, Kyriakides T, Zhu Y, Sessa WC, Pardi R, Bender JR. Macrophage β2 Integrin–Mediated, HuR-Dependent Stabilization of Angiogenic Factor–Encoding mRNAs in Inflammatory Angiogenesis. American Journal Of Pathology 2012, 180: 1751-1760. PMID: 22322302, PMCID: PMC3349897, DOI: 10.1016/j.ajpath.2011.12.025.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis Inducing AgentsAnimalsCD18 AntigensCell AdhesionCells, CulturedDisease Models, AnimalELAV ProteinsGene Expression RegulationGene Knockout TechniquesHindlimbInflammationIschemiaMacrophagesMiceMice, KnockoutMuscle, SkeletalNeovascularization, PathologicReal-Time Polymerase Chain ReactionRNA, MessengerConceptsKnockout miceAngiogenic factorsT cell cytokine productionIntercellular adhesion molecule-1Blood flow recoveryFemoral artery ligationLittermate wild-type controlsVascular endothelial growth factorBone marrow-derived macrophagesMatrix metalloproteinase-9Adhesion molecule-1Endothelial growth factorMarrow-derived macrophagesSoluble factor productionWild-type controlsArtery ligationLigand intercellular adhesion molecule-1Cytokine productionInflammatory angiogenesisMetalloproteinase-9Tissue ischemiaInflammatory stimuliMolecule-1Macrophage productionNeovascular responsePhospholipid Scramblase 1 Mediates Type I Interferon-Induced Protection against Staphylococcal α-Toxin
Lizak M, Yarovinsky TO. Phospholipid Scramblase 1 Mediates Type I Interferon-Induced Protection against Staphylococcal α-Toxin. Cell Host & Microbe 2012, 11: 70-80. PMID: 22264514, PMCID: PMC3266557, DOI: 10.1016/j.chom.2011.12.004.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBacterial ToxinsBody TemperatureBody WeightCell LineCell SurvivalDisease Models, AnimalEpithelial CellsHemolysin ProteinsHumansInterferon-alphaLipoylationMiceMice, KnockoutPhospholipid Transfer ProteinsProtein Processing, Post-TranslationalStaphylococcal InfectionsStaphylococcus aureusSurvival AnalysisConceptsLung epithelial cellsI interferonΑ-toxinStaphylococcal α-toxinCytolytic activityPhospholipid scramblase 1Epithelial cellsInnate protective mechanismsCause of pneumoniaHuman lung epithelial cellsType I interferonAureus clinical isolatesPore-forming toxinsMajor virulence factorScramblase 1Intracellular ATP depletionPositive pathogen Staphylococcus aureusMice displayClinical isolatesAureus strainsProtective mechanismCellular depletionBacterial pore-forming toxinsVirulence factorsUnderlying mechanism
2007
Interferons Increase Cell Resistance to Staphylococcal Alpha-Toxin
Yarovinsky TO, Monick MM, Husmann M, Hunninghake GW. Interferons Increase Cell Resistance to Staphylococcal Alpha-Toxin. Infection And Immunity 2007, 76: 571-577. PMID: 18070901, PMCID: PMC2223481, DOI: 10.1128/iai.01088-07.Peer-Reviewed Original ResearchConceptsStaphylococcal infectionsIFN-alphaTumor necrosis factor alphaNecrosis factor alphaStaphylococcal alpha toxinFatty acid synthase activityCell resistancePore-forming toxinsProinflammatory mediatorsIL-6IL-4Factor alphaInterleukin-1betaIFN-gammaImportant virulence factorAlpha toxinDepletion of ATPIFN-betaProtective roleLipid metabolismMitogen-activated protein kinaseCaspase-1InterferonHost factorsPrior exposure