2023
Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis
Ozmen A, Nwabuobi C, Tang Z, Guo X, Larsen K, Guller S, Blas J, Moore M, Kayisli U, Lockwood C, Guzeloglu-Kayisli O. Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis. International Journal Of Molecular Sciences 2023, 25: 135. PMID: 38203306, PMCID: PMC10778808, DOI: 10.3390/ijms25010135.Peer-Reviewed Original ResearchMeSH KeywordsFemaleHumansInterleukin-6LeptinNF-kappa BPlacentaPre-EclampsiaPregnancySTAT5 Transcription FactorConceptsIL-6 expressionHofbauer cellsP65 NF-κBIL-6NF-κBLeptin levelsPreeclampsia pathogenesisElevated serum interleukin-6 levelsSerum interleukin-6 levelsERK1/2 MAPKInterleukin-6 levelsPro-inflammatory phenotypeAnti-inflammatory phenotypeLeptin receptor expressionIL-6 productionPathogenesis of PEPlacental leptin productionPhosphorylation levelsERK1/2 MAPK inhibitorIL-6 regulationConcentration-dependent mannerPE patientsHuman pregnancySecond trimesterLeptin concentrations
2018
Excess glucose induce trophoblast inflammation and limit cell migration through HMGB1 activation of Toll‐Like receptor 4
Heim KR, Mulla MJ, Potter JA, Han CS, Guller S, Abrahams VM. Excess glucose induce trophoblast inflammation and limit cell migration through HMGB1 activation of Toll‐Like receptor 4. American Journal Of Reproductive Immunology 2018, 80: e13044. PMID: 30175447, DOI: 10.1111/aji.13044.Peer-Reviewed Original ResearchConceptsToll-like receptor 4High mobility group box 1Damage-associated molecular patternsHMGB1 activationIL-1βIL-8Trophoblast responsesReceptor 4Human first trimester trophoblast cell lineFirst trimester trophoblast cell lineInflammatory IL-8Risk of preeclampsiaGroup box 1Uric acidIL-1β responseExcess glucoseTrophoblast cell lineCell migrationTrophoblast inflammationPregnancy outcomesTLR4 antagonistLPS-RSIL-6SFlt-1HMGB1 inhibitor
2017
Dynamics of Base Excision Repair at the Maternal–Fetal Interface in Pregnancies Complicated by Preeclampsia
Tadesse S, Norwitz NG, Guller S, Arcuri F, Toti P, Norwitz ER, Kidane D. Dynamics of Base Excision Repair at the Maternal–Fetal Interface in Pregnancies Complicated by Preeclampsia. Reproductive Sciences 2017, 24: 856-864. PMID: 27707956, DOI: 10.1177/1933719116670519.Peer-Reviewed Original ResearchConceptsMaternal-fetal interfaceOxidative stressNormotensive controlsPlacental tissueHypoxia/reperfusion (H/R) modelPlacental endothelial dysfunctionPlacentas of womenHealthy control subjectsApyrimidinic endonuclease 1PE placental tissuesPregnancy ComplicatedEndothelial dysfunctionPreeclamptic womenPerinatal mortalityReperfusion modelControl subjectsDecidual cellsPathological basisVivo comparative studyPreeclampsiaMaternal cellsFetal cellsAPE1 expressionSignificant increaseWomen
2016
Inflammatory processes are specifically enhanced in endothelial cells by placental-derived TNF-α: Implications in preeclampsia (PE)
Shaw J, Tang Z, Schneider H, Saljé K, Hansson SR, Guller S. Inflammatory processes are specifically enhanced in endothelial cells by placental-derived TNF-α: Implications in preeclampsia (PE). Placenta 2016, 43: 1-8. PMID: 27324092, DOI: 10.1016/j.placenta.2016.04.015.Peer-Reviewed Original ResearchConceptsPro-inflammatory cytokine secretionMaternal perfusateCytokine secretionEndothelial dysfunctionActivation markersEndothelial cellsTNF-α blocking antibodyDual perfusion modelMaternal endothelial dysfunctionPro-inflammatory cytokinesMCP-1 secretionTNF-α actionEndothelial cell linePlacental pathophysiologyEndothelial activationIL-6IL-8Maternal endotheliumInflammatory processDual perfusionMaternal circulationBlocking antibodiesPreeclampsiaTNFPerfusion model
2014
Syncytiotrophoblast Vesicles Show Altered micro-RNA and Haemoglobin Content after Ex-vivo Perfusion of Placentas with Haemoglobin to Mimic Preeclampsia
Cronqvist T, Saljé K, Familari M, Guller S, Schneider H, Gardiner C, Sargent IL, Redman CW, Mörgelin M, Åkerström B, Gram M, Hansson SR. Syncytiotrophoblast Vesicles Show Altered micro-RNA and Haemoglobin Content after Ex-vivo Perfusion of Placentas with Haemoglobin to Mimic Preeclampsia. PLOS ONE 2014, 9: e90020. PMID: 24587192, PMCID: PMC3937405, DOI: 10.1371/journal.pone.0090020.Peer-Reviewed Original ResearchConceptsPathology of preeclampsiaCell-free HbMiR-517bMiR-517aSyncytiotrophoblast vesiclesExtracellular free hemoglobinPerfusion of placentaEx vivo perfusion systemMicro-RNAsMaternal circulationMimic preeclampsiaMaternal sidePerfusion mediumFree hemoglobinHuman placentaPerfusion phaseSurface markersPlacentaMiR-141Hemoglobin contentPerfusionPerfusion systemPreeclampsiaHemoglobinQuantitative PCRIn Vivo and In Vitro Evidence for Placental DNA Damage in Preeclampsia
Tadesse S, Kidane D, Guller S, Luo T, Norwitz NG, Arcuri F, Toti P, Norwitz ER. In Vivo and In Vitro Evidence for Placental DNA Damage in Preeclampsia. PLOS ONE 2014, 9: e86791. PMID: 24466242, PMCID: PMC3899334, DOI: 10.1371/journal.pone.0086791.Peer-Reviewed Original ResearchConceptsDecidual stromal cellsCytotrophoblast cellsMaternal decidual stromal cellsReactive oxygen speciesPlacental oxidative stressFetal-maternal interfaceDNA damagePE placental tissuesAnti-oxidant defensesMultisystem diseasePregnant womenPE placentasFetal sideMaternal deciduaOxidative DNA damagePreeclampsiaPlacental tissueNormal placentaStromal cellsPlacentaOxidative stressVitro EvidenceRepair responseDNA damage/repair responseΓH2AX foci
2013
Decreased Levels of Folate Receptor‐β and Reduced Numbers of Fetal Macrophages (Hofbauer Cells) in Placentas from Pregnancies with Severe Pre‐Eclampsia
Tang Z, Buhimschi IA, Buhimschi CS, Tadesse S, Norwitz E, Niven‐Fairchild T, Huang S, Guller S. Decreased Levels of Folate Receptor‐β and Reduced Numbers of Fetal Macrophages (Hofbauer Cells) in Placentas from Pregnancies with Severe Pre‐Eclampsia. American Journal Of Reproductive Immunology 2013, 70: 104-115. PMID: 23480364, PMCID: PMC3686834, DOI: 10.1111/aji.12112.Peer-Reviewed Original ResearchConceptsSpontaneous preterm birthPre-eclampsiaAge-matched normotensive controlsPreterm pre-eclampsiaSevere pre eclampsiaPathophysiology of PEPregnancy complicationsPreterm birthNormotensive controlsHofbauer cellsFetal mortalityUnknown etiologyPlacental expressionSPTB groupMacrophage functionPlacentaSevere preFetal macrophagesWestern blottingMajor causeProtein expressionPlacental genesReverse transcription-PCR analysisMarker mRNAsTranscription-PCR analysis
2010
Protein composition of microparticles shed from human placenta during placental perfusion: Potential role in angiogenesis and fibrinolysis in preeclampsia
Guller S, Tang Z, Ma YY, Di Santo S, Sager R, Schneider H. Protein composition of microparticles shed from human placenta during placental perfusion: Potential role in angiogenesis and fibrinolysis in preeclampsia. Placenta 2010, 32: 63-69. PMID: 21074265, PMCID: PMC3762591, DOI: 10.1016/j.placenta.2010.10.011.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitorMaternal perfusateSFlt-1Maternal endothelial cell dysfunctionFms-like tyrosine kinasePathophysiology of preeclampsiaMaternal-fetal interfaceEndothelial cell dysfunctionAnti-angiogenic actionFollowing relative levelsPlacental damagePlacental perfusionMaternal serumNormal pregnancyPlacental pathophysiologyAnnexin V bindingSyncytiotrophoblast microparticlesDual perfusionAngiogenic balanceCell dysfunctionMaternal bloodPreeclampsiaActivator inhibitorCytometric analysisLevel of expression
2009
Role of the syncytium in placenta-mediated complications of preeclampsia
Guller S. Role of the syncytium in placenta-mediated complications of preeclampsia. Thrombosis Research 2009, 124: 389-392. PMID: 19535132, PMCID: PMC2764997, DOI: 10.1016/j.thromres.2009.05.016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGiant CellsHumansPlacentaPre-EclampsiaPregnancyPregnancy Complications, HematologicConceptsPlasminogen activator inhibitor-1Fms-like tyrosine kinase-1Complications of preeclampsiaIntrauterine growth restrictionPathophysiology of preeclampsiaTyrosine kinase-1Immune cell functionAnti-angiogenic factorsActivator inhibitor-1Potential protective actionMaternal hemostasisSoluble endoglinEndothelial functionReperfusion injuryMaternal endotheliumMaternal mortalityRelease of microparticlesGrowth restrictionMaternal bloodPreeclampsiaSensitive markerMajor causeInhibitor-1Protective actionReactive oxygen species
2008
Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia
Guller S, Buhimschi CS, Y Y, Huang T, Yang L, Kuczynski E, Zambrano E, Lockwood CJ, Buhimschi IA. Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia. Laboratory Investigation 2008, 88: 1057-1067. PMID: 18679377, PMCID: PMC2682720, DOI: 10.1038/labinvest.2008.74.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Severe preeclampsiaReperfusion injurySFlt-1Soluble fms-like tyrosine kinase-1Fms-like tyrosine kinase-1Ischemia/reperfusion injuryLife-threatening syndromeSubsequent reperfusion injuryTerm control groupPathophysiology of preeclampsiaTyrosine kinase-1Activator inhibitor-1Release of factorsSignificant increasePresence of mRNAUpregulation of mRNACeruloplasmin mRNAPlacental damagePlacental factorsMicroarray gene profilingEndothelium dysfunctionPE placentasQuantitative real-time PCRIntervillous spaceThe Placental Syncytium and the Pathophysiology of Preeclampsia and Intrauterine Growth Restriction
Guller S, Y. Y, Fu H, Krikun G, Abrahams VM, Mor G. The Placental Syncytium and the Pathophysiology of Preeclampsia and Intrauterine Growth Restriction. Annals Of The New York Academy Of Sciences 2008, 1127: 129-133. PMID: 18443340, PMCID: PMC3671376, DOI: 10.1196/annals.1434.015.Peer-Reviewed Original ResearchConceptsIntrauterine growth restrictionPathophysiology of preeclampsiaGrowth restrictionPlacental syncytiumFms-like tyrosine kinase-1Complications of pregnancyPlasminogen activator inhibitor-1Tyrosine kinase-1Activator inhibitor-1Release of factorsPlacental damageSoluble endoglinEndothelium dysfunctionLaser capture microdissectionMaternal bloodAntiangiogenic factorsPreeclampsiaFas ligandWestern blottingInhibitor-1Reactive oxygen speciesCapture microdissectionPregnancyPathophysiologyKinase 1
2006
Differential Release of Plasminogen Activator Inhibitors (PAIs) During Dual Perfusion of Human Placenta: Implications in Preeclampsia
Guller S, Ma Y, Malek A, Di Santo S, Schneider H. Differential Release of Plasminogen Activator Inhibitors (PAIs) During Dual Perfusion of Human Placenta: Implications in Preeclampsia. Placenta 2006, 28: 278-285. PMID: 16820203, DOI: 10.1016/j.placenta.2006.05.005.Peer-Reviewed Original ResearchConceptsIntrauterine growth restrictionPAI-1 levelsPlasminogen activator inhibitorTotal PAI-1 levelsMaternal perfusateDual perfusionTime-dependent increaseReactive oxygen speciesRelease of PAIActivator inhibitorIntervillous fibrin depositionActive PAI-1 levelsSignificant time-dependent increasePAI-2 levelsPAI-1 releaseHuman term placentaPlacental tissue extractsAberrant fibrinolysisPlacental infarctionMaternal serumFibrin depositionGrowth restrictionIntervillous spacePreeclampsiaTerm placentaFractional Excretion of Angiogenic Factors in Women With Severe Preeclampsia
Buhimschi CS, Magloire L, Funai E, Norwitz ER, Kuczynski E, Martin R, Richman S, Guller S, Lockwood CJ, Buhimschi IA. Fractional Excretion of Angiogenic Factors in Women With Severe Preeclampsia. Obstetrics And Gynecology 2006, 107: 1103-1113. PMID: 16648417, DOI: 10.1097/01.aog.0000207698.74104.4f.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorPlacental growth factorEndothelial growth factorProtein/creatinine ratioTotal protein/creatinine ratioPreeclamptic womenFractional excretionSevere preeclampsiaCreatinine ratioSFlt-1Angiogenic factorsGrowth factorPregnant controlsSoluble fms-like tyrosine kinase-1Serum placental growth factor levelsUrinary vascular endothelial growth factorFms-like tyrosine kinase-1Placental growth factor levelsHealthy pregnant controlsHealthy pregnant womenDisease clinical manifestationsGrowth factor levelsTyrosine kinase-1Preeclamptic groupRenal production
2005
Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia
Buhimschi CS, Norwitz ER, Funai E, Richman S, Guller S, Lockwood CJ, Buhimschi IA. Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia. American Journal Of Obstetrics And Gynecology 2005, 192: 734-741. PMID: 15746665, DOI: 10.1016/j.ajog.2004.12.052.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorSevere preeclampsiaHypertensive disordersHypertensive womenUrinary levelsUrinary outputSFlt-1Soluble fms-like tyrosine kinase-1Fms-like tyrosine kinase-1Antiangiogenic factors sFlt-1Growth factorSFlt-1 concentrationsHealthy pregnant controlsPlacental growth factorTime of enrollmentTyrosine kinase-1Urinary protein measurementsEndothelial growth factorClinical preeclampsiaProteinuric womenPlGF levelsNonpregnant womenPlGF ratioPregnant controlsGestational age