Featured Publications
Smooth 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 damageA Novel Dual-Function Nitric Oxide Donor Therapy for Preeclampsia—A Proof-of-Principle Study in a Murine Model
Pintye D, Sziva R, Biwer L, Karreci E, Jacas S, Mastyugin M, Török M, Young B, Jagtap P, Southan G, Jaffe I, Zsengellér Z. A Novel Dual-Function Nitric Oxide Donor Therapy for Preeclampsia—A Proof-of-Principle Study in a Murine Model. Antioxidants 2023, 12: 2036. PMID: 38136156, PMCID: PMC10741224, DOI: 10.3390/antiox12122036.Peer-Reviewed Original ResearchBlood pressureOxidative stressNitric oxide donor therapyPlasma cystatin C.Plasma nitrate levelsHealthy female miceModel of preeclampsiaNitric oxide bioavailabilityEx vivo treatmentPotential therapeutic effectsReduced oxidative stressNovel therapeutic agentsDays of treatmentAnti-angiogenic responseDonor therapyPlacental damageReduced hypertensionHypertensive disordersSubstantial morbidityFetal pathophysiologyResistance vesselsGlomerular endotheliosisPE symptomsVascular disordersFemale miceNon–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
2019
Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning
Willeman M, Chawla M, Zempare M, Biwer L, Hoang L, Uprety A, Fitzhugh M, De Both M, Coleman P, Trouard T, Alexander G, Mitchell K, Barnes C, Hale T, Huentelman M. Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning. Physiological Reports 2019, 7: e14010. PMID: 30916484, PMCID: PMC6436186, DOI: 10.14814/phy2.14010.Peer-Reviewed Original ResearchConceptsTransgenic ratsBlood pressureCyp1a1-Ren2 transgenic ratsRenin-dependent hypertensionImpact of hypertensionInduction of hypertensionSystolic blood pressureTransgenic rat modelMajor health concernAge of onsetRenal hypertrophyPrevalence increasesHypertension inductionRat modelHypertensionNeurological healthCollagen depositionLeft ventricleSensory functionBrain regionsCardiovascular systemSignificant impairmentRate of inductionMorris swim taskRats
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
Loss of endothelial Fto is protective against metabolic disease
Krüger N, Biwer L, Good M, Rüther U, Isakson B. Loss of endothelial Fto is protective against metabolic disease. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.1015.15.Peer-Reviewed Original ResearchHigh-fat dietObesity-induced metabolic changesHFD-fed miceMyogenic toneBlood pressureNormal chowMesenteric arteryResistance arteriesEndothelial cellsMetabolic changesNC-fed miceObesity-induced hypertensionSerum lipid levelsOrder mesenteric arteriesSerum lipid analysisFto-deficient miceVascular healthVascular levelVascular toneInsulin resistanceInsulin toleranceFat dietPathophysiological changesDeficient miceFat mass
2016
Endothelial 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
2015
Time course of cardiac inflammation during nitric oxide synthase inhibition in SHR: impact of prior transient ACE inhibition
Biwer L, D'souza K, Abidali A, Tu D, Siniard A, DeBoth M, Huentelman M, Hale T. Time course of cardiac inflammation during nitric oxide synthase inhibition in SHR: impact of prior transient ACE inhibition. Hypertension Research 2015, 39: 8-18. PMID: 26490086, DOI: 10.1038/hr.2015.107.Peer-Reviewed Original ResearchConceptsTransient ACE inhibitionNAME treatmentPulse pressureNOS inhibitionACE inhibitionCardiac remodelingInterleukin-6Nitric oxide synthase inhibitionCytokine/chemokine levelsNitric oxide synthase inhibitorMonocyte chemoattractant protein-1Adult male SHRChemokine release profileOxide synthase inhibitionOxide synthase inhibitorChemoattractant protein-1Arginine methyl esterPathological cardiac remodelingChemokine levelsMale SHRCardiac inflammationArterial pressureBlood pressureHypertensive ratsIL-10