Featured Publications
Prior Exposure to Experimental Preeclampsia Increases Atherosclerotic Plaque Inflammation in Atherogenic Mice—Brief Report
Biwer L, Man J, Camarda N, Carvajal B, Karumanchi S, Jaffe I. Prior Exposure to Experimental Preeclampsia Increases Atherosclerotic Plaque Inflammation in Atherogenic Mice—Brief Report. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: 946-953. PMID: 38450510, PMCID: PMC10978246, DOI: 10.1161/atvbaha.123.320474.Peer-Reviewed Original ResearchConceptsAtherosclerotic plaque inflammationLDLr-KO micePlaque inflammationAortic root plaque sizeEvidence of premature atherosclerosisFlow cytometryRisk factorsHistory of preeclampsiaIncreased risk of myocardial infarctionPreexisting risk factorsRisk of myocardial infarctionFed high-fat dietExpression of IGFBP6Mouse atherosclerosis modelHigh-density lipoproteinAortic cytokinesNecrotic core areaPreeclampsia exposureSerum sFlt1Normotensive pregnanciesHigh-fat dietPreeclampsia pregnanciesCD3+T cellsHigh-fat feedingLow-density lipoproteinSmooth Muscle Mineralocorticoid Receptor Promotes Hypertension After Preeclampsia
Biwer L, Lu Q, Ibarrola J, Stepanian A, Man J, Carvajal B, Camarda N, Zsengeller Z, Skurnik G, Seely E, Karumanchi S, Jaffe I. Smooth Muscle Mineralocorticoid Receptor Promotes Hypertension After Preeclampsia. Circulation Research 2023, 132: 674-689. PMID: 36815487, PMCID: PMC10119809, DOI: 10.1161/circresaha.122.321228.Peer-Reviewed Original ResearchConceptsBlood pressureSMC-MRHypertensive stimuliBP responseSmooth Muscle Cell Mineralocorticoid ReceptorsAngII type 1 receptorType 1 receptor expressionMR transcriptional activityIncreased cardiovascular riskElevated blood pressureEnd-organ damageHigh salt intakeHigh blood pressureRisk of hypertensionType 1 receptorSoluble VEGF receptorAngII infusionPrior preeclampsiaMR antagonismCardiovascular riskNormotensive pregnanciesSalt dietAortic stiffnessSalt intakeOrgan damageLoss of Endothelial FTO Antagonizes Obesity-Induced Metabolic and Vascular Dysfunction
Krüger N, Biwer L, Good M, Ruddiman C, Wolpe A, DeLalio L, Murphy S, Macal E, Ragolia L, Serbulea V, Best A, Leitinger N, Harris T, Sonkusare S, Gödecke A, Isakson B. Loss of Endothelial FTO Antagonizes Obesity-Induced Metabolic and Vascular Dysfunction. Circulation Research 2019, 126: 232-242. PMID: 31801409, PMCID: PMC7007767, DOI: 10.1161/circresaha.119.315531.Peer-Reviewed Original ResearchConceptsMyogenic toneProstaglandin DResistance arteriesDeficient miceHigh-fat diet-induced glucose intoleranceDiet-induced glucose intoleranceObesity-induced hypertensionImpact of obesityPrevalence of obesityNew treatment optionsDevelopment of obesityHigh-fat dietRegulation of obesityDifferent cell typesCell typesGlucose intoleranceVascular alterationsVascular changesVascular dysfunctionControl miceInsulin resistanceTreatment optionsCardiovascular diseaseObesityArteryNon–Endoplasmic Reticulum–Based Calr (Calreticulin) Can Coordinate Heterocellular Calcium Signaling and Vascular Function
Biwer L, Good M, Hong K, Patel R, Agrawal N, Looft-Wilson R, Sonkusare S, Isakson B. Non–Endoplasmic Reticulum–Based Calr (Calreticulin) Can Coordinate Heterocellular Calcium Signaling and Vascular Function. Arteriosclerosis Thrombosis And Vascular Biology 2017, 38: 120-130. PMID: 29122814, PMCID: PMC5746467, DOI: 10.1161/atvbaha.117.309886.Peer-Reviewed Original ResearchConceptsThird-order mesenteric arteriesBlood pressureMesenteric arteryVascular functionCalcium signalingIEL holesApplication of CChMyoendothelial junctionsCalcium eventsER calciumSmooth muscle cellsInternal elastic laminaVascular reactivityResistance arteriesSmall arteriesSame arteryKnockout miceArteryΔ miceElastic laminaMuscle cellsEndoplasmic reticulum calciumMiceCALRCalcium signals
2022
Smooth muscle cell FTO regulates contractile function
Luse M, Krüger N, Good M, Biwer L, Serbulea V, Salamon A, Deaton R, Leitinger N, Gödecke A, Isakson B. Smooth muscle cell FTO regulates contractile function. AJP Heart And Circulatory Physiology 2022, 323: h1212-h1220. PMID: 36306211, PMCID: PMC9678421, DOI: 10.1152/ajpheart.00427.2022.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsThird-order mesenteric arteriesMuscle cellsObesity genesSmooth muscle contractilityRates of obesityHuman coronary arteriesCardiac myocyte contractilityPlasma reninBlood pressureMesenteric arteryMyogenic toneCoronary arteryFat massContractile functionMyocyte contractilityMuscle contractilityHeart rateSerum response factorMuscle depolarizationMouse body massContractilitySignificant decreaseCell deletionMice
2018
Vascular Mineralocorticoid Receptor: Evolutionary Mediator of Wound Healing Turned Harmful by Our Modern Lifestyle
Biwer L, Wallingford M, Jaffe I. Vascular Mineralocorticoid Receptor: Evolutionary Mediator of Wound Healing Turned Harmful by Our Modern Lifestyle. American Journal Of Hypertension 2018, 32: 123-134. PMID: 30380007, PMCID: PMC6331708, DOI: 10.1093/ajh/hpy158.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiovascular DiseasesDiet, High-FatEndothelial CellsEndothelium, VascularEvolution, MolecularHemodynamicsHumansLife StyleMuscle, Smooth, VascularMyocytes, Smooth MuscleReceptors, MineralocorticoidRisk FactorsSedentary BehaviorSignal TransductionSodium, DietaryVascular RemodelingWound HealingConceptsVascular mineralocorticoid receptorMineralocorticoid receptorActivation of MRDiffuse vascular damageMechanical vascular injuryHigh sodium dietBlood pressure maintenanceVascular tone regulationSmooth muscle cellsSodium dietBlood pressureMR activationVascular damagePhysical inactivityVascular injuryAdvanced ageTone regulationCardiovascular diseaseVascular remodelingSurvival advantageElectrolyte homeostasisVascular wallMuscle cellsModern lifestyleMR function
2017
A Cell Culture Model of Resistance Arteries.
Biwer L, Lechauve C, Vanhoose S, Weiss M, Isakson B. A Cell Culture Model of Resistance Arteries. Journal Of Visualized Experiments 2017 PMID: 28930992, PMCID: PMC5752193, DOI: 10.3791/55992.Peer-Reviewed Original ResearchConceptsCell culture modelCell typesMyoendothelial junctionsEndothelial cell polarizationPlating of cellsIntact cell layerDifferent cell typesSignaling microdomainCulture modelSpecific proteinsCell polarizationPhysiological relevanceActivity assaysProtein isolationSmooth muscle cellsVascular cellsMuscle cellsImmunofluorescent analysisIntact resistance arteriesProteinCellsMuscle fractionsIsolationCell layerVCCC
2016
Two functionally distinct pools of eNOS in endothelium are facilitated by myoendothelial junction lipid composition
Biwer L, Taddeo E, Kenwood B, Hoehn K, Straub A, Isakson B. Two functionally distinct pools of eNOS in endothelium are facilitated by myoendothelial junction lipid composition. Biochimica Et Biophysica Acta 2016, 1861: 671-679. PMID: 27106139, PMCID: PMC4869716, DOI: 10.1016/j.bbalip.2016.04.014.Peer-Reviewed Original ResearchMeSH KeywordsBiological TransportBradykininCalciumCalcium SignalingCell CommunicationCoculture TechniquesCyclic GMPDiglyceridesEgtazic AcidEndoplasmic ReticulumEndothelial CellsGap JunctionsGene Expression RegulationHumansInositol 1,4,5-TrisphosphateMacrocyclic CompoundsMyocytes, Smooth MuscleNitric Oxide Synthase Type IIIOxazolesPhenylephrinePhosphatidylserinesPhosphorylationPrimary Cell CultureProtein Kinase CProtein Kinase InhibitorsThapsigargin
2015
Endothelial nitric oxide synthase in the microcirculation
Shu X, Keller T, Begandt D, Butcher J, Biwer L, Keller A, Columbus L, Isakson B. Endothelial nitric oxide synthase in the microcirculation. Cellular And Molecular Life Sciences 2015, 72: 4561-4575. PMID: 26390975, PMCID: PMC4628887, DOI: 10.1007/s00018-015-2021-0.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNitric oxide synthaseOxide synthaseAnti-inflammatory mediatorsRegulation of eNOSRed blood cellsMicrovascular effectsVessel toneImmune responsePharmacological agentsENOS enzymeNitric oxideBlood cellsNO actionKey moleculesENOSVariety of effectsPhysiological roleCellsVasodilatorsSynthaseMicrocirculation
2014
Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall
Billaud M, Lohman A, Johnstone S, Biwer L, Mutchler S, Isakson B. Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall. Pharmacological Reviews 2014, 66: 513-569. PMID: 24671377, PMCID: PMC3973613, DOI: 10.1124/pr.112.007351.Peer-Reviewed Original ResearchConceptsCellular communicationAccumulation of proteinsMechanism of exocytosisSignaling microdomainProper vascular functionPlasma membraneBlood vessel wallCell typesIon channelsMicrodomainsGap junctionsOxygen speciesPotassium channelsVon Willebrand factorPlethora of meansRegulationSpecific regionsEssential componentVessel wall functionWillebrand factorParacrine releaseImportant roleVessel wallExocytosisEndothelium-derived hyperpolarization