2023
Guidelines 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 ResearchEffects of androgen excess and body mass index on endothelial function in women with polycystic ovary syndrome
Berbrier D, Leone C, Adler T, Bender J, Taylor H, Stachenfeld N, Usselman C. Effects of androgen excess and body mass index on endothelial function in women with polycystic ovary syndrome. Journal Of Applied Physiology 2023, 134: 868-878. PMID: 36861670, DOI: 10.1152/japplphysiol.00583.2022.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeEndothelial dysfunctionEndothelial functionOvary syndromeAndrogen excessLean womenObese womenEstradiol supplementationLow flow-mediated constrictionOW/OB groupOverweight/obese womenMarked endothelial dysfunctionSevere endothelial dysfunctionFree testosterone levelsBody mass indexFlow-mediated dilation (FMD) testFree testosteroneMass indexReactive hyperemiaOB groupTestosterone levelsHealth differEndothelial pathophysiologyDysfunctionAndrogens
2019
CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation
Esteghamat F, Broughton JS, Smith E, Cardone R, Tyagi T, Guerra M, Szabó A, Ugwu N, Mani MV, Azari B, Kayingo G, Chung S, Fathzadeh M, Weiss E, Bender J, Mane S, Lifton RP, Adeniran A, Nathanson MH, Gorelick FS, Hwa J, Sahin-Tóth M, Belfort-DeAguiar R, Kibbey RG, Mani A. CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation. Nature Genetics 2019, 51: 1233-1243. PMID: 31358993, PMCID: PMC6675645, DOI: 10.1038/s41588-019-0470-3.Peer-Reviewed Original ResearchConceptsEarly-onset atherosclerosisMetabolic syndromeMetabolic syndrome traitsWhole-exome sequence analysisAttractive therapeutic targetPlatelet hyperactivationInsulin levelsPlasma insulinPlasma levelsInsulin sensitivityInsulin secretionTherapeutic targetPlatelet activationDisease mechanismsSyndrome traitsAtherosclerosisFunction mutationsSyndromeNovel lossInsulinMutationsSecretionAndrogens 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
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 molecular actions of oestrogen in the regulation of vascular health
Usselman CW, Stachenfeld NS, Bender JR. The molecular actions of oestrogen in the regulation of vascular health. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2016, 101: 356-361. PMID: 26778523, PMCID: PMC4947570, DOI: 10.1113/ep085148.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAction of estrogenVascular healthFunctional outcomeHormone therapy trialsNormal endothelial functionVascular smooth muscleMembrane-bound estrogen receptorMolecular actionsPremenopausal womenEndothelial functionEstrogen actionCardiovascular diseaseEstrogen receptorSmooth muscleBeneficial actionsTherapy trialsEstrogenExperimental animalsVascular structuresFindings of studiesVasculatureWomenHealthMolecular mechanismsOutcomes
2015
Menopause and the Heart
Nkonde-Price C, Bender JR. Menopause and the Heart. Endocrinology And Metabolism Clinics Of North America 2015, 44: 559-564. PMID: 26316243, DOI: 10.1016/j.ecl.2015.05.005.Peer-Reviewed Original ResearchConceptsPostmenopausal hormone replacement therapyPostmenopausal US womenHormone replacement therapyHormone therapy initiationHealth topicsCause of deathWomen's health topicsTherapy initiationCardiovascular riskOngoing trialsReplacement therapyCardiovascular concernsClinical trialsCardiovascular diseaseUS womenCurrent recommendationsDiscordant resultsTrialsMenopauseTherapyDiseaseWomen
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 stimulationSilver Lining in the Dark Cloud of Aneurysm Disease
Chau KH, Bender JR, Elefteriades JA. Silver Lining in the Dark Cloud of Aneurysm Disease. Cardiology 2014, 128: 327-332. PMID: 24942201, DOI: 10.1159/000358123.Peer-Reviewed Original ResearchConceptsAortic aneurysmCarotid intima-media thicknessIntima-media thicknessClinical findingsArterial calcificationAneurysm diseaseAortic rootClinical dataProtective effectPharmacologic evidenceMatrix metalloproteinasesAneurysmsAtherosclerosisEarly indicatorDiseaseMolecular mechanismsEvidencePatientsSilver liningDiagnosisCalcificationMetalloproteinasesGenetic studiesCeramide-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 homeostasisPhosphorylationEndothelial estrogen receptor isoforms and cardiovascular disease
Kim KH, Young BD, Bender JR. Endothelial estrogen receptor isoforms and cardiovascular disease. Molecular And Cellular Endocrinology 2014, 389: 65-70. PMID: 24530925, PMCID: PMC4040324, DOI: 10.1016/j.mce.2014.02.001.BooksConceptsNitric oxideFull-length ERαPlasma membrane-associated estrogen receptorOvarian steroid hormonesMembrane-associated estrogen receptorsEstrogen receptor isoformsCardiovascular diseaseEstrogen receptorEndothelial responseRapid E2ER isoformsSteroid hormonesReceptor isoformsVascular cellsClinical contextFavorable effectTissue responseEndothelial signalingVascular systemERαER46Transcriptional modulationTransmembrane moleculesSignalingRapid endothelial responses
2013
Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis
Nie L, Guo X, Esmailzadeh L, Zhang J, Asadi A, Collinge M, Li X, Kim JD, Woolls M, Jin SW, Dubrac A, Eichmann A, Simons M, Bender JR, Sadeghi MM. Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis. Journal Of Clinical Investigation 2013, 123: 5082-5097. PMID: 24177422, PMCID: PMC3859420, DOI: 10.1172/jci67752.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBlood VesselsCadherinsCells, CulturedEar, ExternalEndothelium, VascularHindlimbHuman Umbilical Vein Endothelial CellsHumansIschemiaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutNeovascularization, PhysiologicNeuropilinsProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine Phosphatase, Non-Receptor Type 2Retinal VesselsRNA InterferenceRNA, Small InterferingVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ZebrafishZebrafish ProteinsConceptsSmooth muscle cell-derived neuropilin-like proteinAberrant blood vessel formationNormal vascular developmentProtein tyrosineTC-PTPTransmembrane proteinTherapeutic targetBlood vessel formationVEGF responseNegative regulatorDevelopmental angiogenesisVEGFR-2Vascular developmentAttractive therapeutic targetESDNAngiogenesis regulationVE-cadherinVessel formationEC proliferationComplex formationRegulatorProteinNeuropilin expressionVEGF receptorsEndothelial VEGF
2012
Molecular Imaging of Vascular Endothelial Growth Factor Receptors in Graft Arteriosclerosis
Zhang J, Razavian M, Tavakoli S, Nie L, Tellides G, Backer JM, Backer MV, Bender JR, Sadeghi MM. Molecular Imaging of Vascular Endothelial Growth Factor Receptors in Graft Arteriosclerosis. Arteriosclerosis Thrombosis And Vascular Biology 2012, 32: 1849-1855. PMID: 22723442, PMCID: PMC3401339, DOI: 10.1161/atvbaha.112.252510.Peer-Reviewed Original ResearchConceptsGraft arteriosclerosisArtery graftVascular remodelingAllogeneic human peripheral blood mononuclear cellsHuman coronary artery segmentsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsSevere combined immunodeficiency miceVEGF receptorsVascular endothelial growth factor receptorLate organ failureHuman coronary artery graftsSolid organ transplantationCoronary artery graftsEndothelial growth factor receptorBlood mononuclear cellsCoronary artery segmentsCombined immunodeficiency miceReceptor 2 expressionVEGF receptor-2 expressionMolecular imagingSignificant neointima formationVascular endothelial growth factor signalingVEGF receptor 1Growth factor receptor
2011
Splice isoform estrogen receptors as integral transmembrane proteins
Kim KH, Toomre D, Bender JR. Splice isoform estrogen receptors as integral transmembrane proteins. Molecular Biology Of The Cell 2011, 22: 4415-4423. PMID: 21937726, PMCID: PMC3216666, DOI: 10.1091/mbc.e11-05-0416.Peer-Reviewed Original ResearchConceptsSplice isoformsTotal internal reflection fluorescence microscopySteroid hormone receptorsIntegral transmembrane proteinN-terminal ectodomainReflection fluorescence microscopyHormone receptorsTransmembrane proteinPlasma membraneProtein structureHuman endothelial cellsLigand engagementPotential novel therapeutic targetER46Fluorescence microscopyNovel therapeutic targetEcliptic pHluorinActivation signalsEndothelial nitric oxide synthase activationEstrogen receptor αENOS activationReceptor αIsoformsTherapeutic targetNitric oxide synthase activation
2010
T Cell LFA-1 Engagement Induces HuR-Dependent Cytokine mRNA Stabilization through a Vav-1, Rac1/2, p38MAPK and MKK3 Signaling Cascade
Ramgolam VS, DeGregorio SD, Rao GK, Collinge M, Subaran SS, Markovic-Plese S, Pardi R, Bender JR. T Cell LFA-1 Engagement Induces HuR-Dependent Cytokine mRNA Stabilization through a Vav-1, Rac1/2, p38MAPK and MKK3 Signaling Cascade. PLOS ONE 2010, 5: e14450. PMID: 21206905, PMCID: PMC3012057, DOI: 10.1371/journal.pone.0014450.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceCytokinesELAV ProteinsELAV-Like Protein 1GTP PhosphohydrolasesHumansIntegrinsInterferon-gammaLymphocyte Function-Associated Antigen-1MAP Kinase Kinase 3MiceMice, Inbred C57BLNeuropeptidesP38 Mitogen-Activated Protein KinasesProto-Oncogene Proteins c-vavRac GTP-Binding ProteinsRac1 GTP-Binding ProteinRNA-Binding ProteinsSignal TransductionT-LymphocytesTumor Necrosis Factor-alpha
2009
Membrane-initiated actions of estrogen on the endothelium
Kim KH, Bender JR. Membrane-initiated actions of estrogen on the endothelium. Molecular And Cellular Endocrinology 2009, 308: 3-8. PMID: 19549586, PMCID: PMC2701909, DOI: 10.1016/j.mce.2009.03.025.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNumerous signal transduction cascadesSignal transduction cascadeNitric oxideEndothelial cellsNon-genomic actionsAction of estrogenNitric oxide synthaseCaveolar membranesEstrogen receptor alphaTransduction cascadeC-SrcN-terminusShort isoformHuman endothelial cellsRapid activationProduct nitric oxideVascular studiesOxide synthaseReceptor alphaEstrogenVascular structuresER46Favorable effectCritical role
2008
Vascular cell signaling by membrane estrogen receptors
Kim KH, Moriarty K, Bender JR. Vascular cell signaling by membrane estrogen receptors. Steroids 2008, 73: 864-869. PMID: 18325557, PMCID: PMC2519041, DOI: 10.1016/j.steroids.2008.01.008.Peer-Reviewed Original ResearchConceptsNumerous signal transduction cascadesEndothelial nitric oxide synthaseCaveolin-1 interactionSignal transduction cascadeEndothelial cellsNon-genomic actionsTranscriptional regulationPI3K/AktMembrane estrogen receptorsCaveolar membranesTransduction cascadeCell signalingC-SrcN-terminusHuman endothelial cellsRapid activationMolecular studiesConsequent activationVascular cellsNumerous animalsNitric oxideMultiple biological effectsEstrogen receptor alphaFavorable estrogenic effectsER46
2007
COP1D, an alternatively spliced constitutive photomorphogenic-1 (COP1) product, stabilizes UV stress-induced c-Jun through inhibition of full-length COP1
Savio M, Rotondo G, Maglie S, Rossetti G, Bender J, Pardi R. COP1D, an alternatively spliced constitutive photomorphogenic-1 (COP1) product, stabilizes UV stress-induced c-Jun through inhibition of full-length COP1. Oncogene 2007, 27: 2401-2411. PMID: 17968316, DOI: 10.1038/sj.onc.1210892.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBreast NeoplasmsCell LineDown-RegulationEnzyme StabilityHealthHeLa CellsHumansIsoenzymesJNK Mitogen-Activated Protein KinasesKineticsMolecular Sequence DataProteasome Endopeptidase ComplexRNA, MessengerTranscription, GeneticTumor Suppressor Protein p53Ubiquitin-Protein LigasesConceptsFull-length proteinC-JunCullin-RING ligase complexRING finger ubiquitin ligaseProteasome-dependent degradationDominant-negative functionCoiled-coil regionFunction of COP1Post-translational changesP53 protein levelsLigase complexCRL complexesE3 ligasesE3 ligaseUbiquitin ligaseCOP1Ectopic expressionRNA interferenceUV stressElevated c-JunPolyubiquitinationSplice variantsVariant estrogen receptor–c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation
Li L, Hisamoto K, Kim KH, Haynes MP, Bauer PM, Sanjay A, Collinge M, Baron R, Sessa WC, Bender JR. Variant estrogen receptor–c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 16468-16473. PMID: 17921256, PMCID: PMC2034248, DOI: 10.1073/pnas.0704315104.Peer-Reviewed Original ResearchConceptsC-SrcC-Src kinase activityTyrosine kinase c-SrcRapid signal transductionKinase c-SrcC-Src functionC-Src kinaseEndothelial NO synthase activationENOS activationMembrane recruitmentSignal transductionComplex assemblyPlasma membraneKinase activityOestrogen receptor-alpha variantsVenous endothelial cellsER46Pathway activationHormonal stimuliCritical roleArterial responseNO synthase activationSynthase activationStructural requirementsEndothelial cells