Featured Publications
Non–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
2024
Mineralocorticoid Receptors in Vascular Smooth Muscle: Blood Pressure and Beyond
Camarda N, Ibarrola J, Biwer L, Jaffe I. Mineralocorticoid Receptors in Vascular Smooth Muscle: Blood Pressure and Beyond. Hypertension 2024, 81: 1008-1020. PMID: 38426347, PMCID: PMC11023801, DOI: 10.1161/hypertensionaha.123.21358.Peer-Reviewed Original ResearchSmooth muscle cellsSMC-MRMineralocorticoid receptorBlood pressurePulmonary hypertensionHeart failureVascular calcificationAngiotensin II type 1 receptorRegulation of vasomotor functionVascular smooth muscleMR knockout miceType 1 receptorAortic valve diseaseSystemic blood pressureSMC proliferationConnective tissue growth factorMatrix metallopeptidase-2Heart valve dysfunctionDiverse cardiovascular disordersResponse to hypertensionTissue growth factorIn vitro studiesIn vivo findingsMyogenic toneValve dysfunction
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
2021
Mineralocorticoid Receptor in Smooth Muscle Contributes to Pressure Overload–Induced Heart Failure
Kim S, Biwer L, Moss M, Man J, Aronovitz M, Martin G, Carrillo-Salinas F, Salvador A, Alcaide P, Jaffe I. Mineralocorticoid Receptor in Smooth Muscle Contributes to Pressure Overload–Induced Heart Failure. Circulation Heart Failure 2021, 14: e007279. PMID: 33517669, PMCID: PMC7887087, DOI: 10.1161/circheartfailure.120.007279.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsMR-intact littermatesAdverse cardiac remodelingMineralocorticoid receptorCardiac remodelingSMC-MRAortic constrictionPressure Overload-Induced Heart FailureInhibition of MRRole of MRPressure overload-induced hypertrophyCardiac blood supplyHeart failure hospitalizationCardiac capillary densityCoronary flow reserveTransverse aortic constrictionIntracardiac pressure measurementsOverload-induced hypertrophyFibrotic gene expressionFetal gene expressionFailure hospitalizationExercise capacityExercise testingEjection fractionHeart failure
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 layerVCCCCalreticulin localized to the myoendothelial junction mediates heterocellular communication in resistance arteries
Biwer L, Good M, Hong K, Patel R, Agrawal N, Looft‐Wilson R, Sonkusare S, Isakson B. Calreticulin localized to the myoendothelial junction mediates heterocellular communication in resistance arteries. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.681.12.Peer-Reviewed Original ResearchEndoplasmic reticulumHeterocellular communicationSmooth muscle cellsER retention signal KDELMyoendothelial junctionsExpression of ERCa 2Proteomic screenConditional knockout micePresence of calreticulinSecond messengerCell extensionsER-TrackerBidirectional signalingBinding proteinCalcium binding proteinSignificant enrichmentCalreticulinER calciumAgonist stimulationCytoplasmic contactMuscle cellsProteinKnockout miceSmooth muscle agonists
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 InhibitorsThapsigarginVascular effects of alpha hemoglobin stabilizing protein deletion
Biwer L, Lechauve C, Billaud M, Weiss M, Isakson B. Vascular effects of alpha hemoglobin stabilizing protein deletion. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.1276.3.Peer-Reviewed Original ResearchSmooth muscle cellsEndothelial cellsMyoendothelial junctionsNeighboring smooth muscle cellsMean arterial pressureBlood pressure measurementsAlpha hemoglobinConcentration-dependent mannerAvailable nitric oxideArterial pressureVascular effectsResistance arteriesKnockout miceENOS interactionMuscle cellsNitric oxideHemoglobin HENOSMiceNational InstitutePercent distributionHemoglobinPressure measurementsHemoglobin betaPLA signalsLipid composition of the myoendothelial junction allows for compartmentalized eNOS function
Biwer L, Taddeo E, Hoehn K, Straub A, Isakson B. Lipid composition of the myoendothelial junction allows for compartmentalized eNOS function. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.727.9.Peer-Reviewed Original ResearchEndothelial nitric oxide synthaseSmooth muscle cellsEndothelial cellsMyoendothelial junctionsResistance arteriesEC endothelial nitric oxide synthaseNeighboring smooth muscle cellsTumor necrosis factor alphaBlood pressure regulationNecrosis factor alphaNitric oxide synthasePKC activityHuman smooth muscle cellsInternal elastic laminaER calcium releaseTHP-1 monocytesCo-cultured endothelial cellsVascular toneENOS functionOxide synthaseFactor alphaGap junction inhibitionLipid compositionDifferential lipid compositionPhenylephrineEndothelial calreticulin and its role in vascular function
Biwer L, Good M, Sonkusare S, Isakson B. Endothelial calreticulin and its role in vascular function. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.955.3.Peer-Reviewed Original ResearchBlood pressureResistance arteriesSmooth muscle cellsER calcium releaseEndothelial cellsMyoendothelial junctionsVascular toneCalcium releaseIntact resistance arteriesPercentage of CD31Microvascular endothelial cellsInternal elastic laminaKnockdown of calreticulinAcute injectionPressure myographyCalcium binding proteinControl miceTamoxifen injectionVascular functionCD31 antibodyKnockout miceCalcium transientsAnatomical hallmarksElastic laminaMuscle cells