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 damageMineralocorticoid and Estrogen Receptors in Endothelial Cells Coordinately Regulate Microvascular Function in Obese Female Mice
Biwer L, Carvajal B, Lu Q, Man J, Jaffe I. Mineralocorticoid and Estrogen Receptors in Endothelial Cells Coordinately Regulate Microvascular Function in Obese Female Mice. Hypertension 2021, 77: 2117-2126. PMID: 33934622, PMCID: PMC8119365, DOI: 10.1161/hypertensionaha.120.16911.Peer-Reviewed Original ResearchEndothelial calreticulin deletion impairs endothelial function in aged mice
Biwer L, Askew-Page H, Hong K, Milstein J, Johnstone S, Macal E, Good M, Bagher P, Sonkusare S, Isakson B. Endothelial calreticulin deletion impairs endothelial function in aged mice. AJP Heart And Circulatory Physiology 2020, 318: h1041-h1048. PMID: 32196361, PMCID: PMC7346539, DOI: 10.1152/ajpheart.00586.2019.Peer-Reviewed Original ResearchConceptsVascular functionTauroursodeoxycholic acidMesenteric arteryAged miceCalcium signalsImpaired endothelial-dependent vasodilationThird-order mesenteric arteriesEndothelial cellsEndothelial-dependent vasodilationIncubation of arteriesImpairs endothelial functionSmall resistance arteriesMultifunctional calcium binding proteinER stress inhibitor tauroursodeoxycholic acidWk of ageEndoplasmic reticulum stressPE constrictionEndothelial functionVasodilatory functionResistance arteriesCalcium binding proteinAgonist carbacholClinical trialsMuscarinic stimulationVasodilationLoss 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 diseaseObesityArtery
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
A venous-specific purinergic signaling cascade initiated by Pannexin 1 regulates TNFα-induced increases in endothelial permeability
Maier-Begandt D, Comstra H, Molina S, Krüger N, Ruddiman C, Chen Y, Chen X, Biwer L, Johnstone S, Lohman A, Good M, DeLalio L, Hong K, Bacon H, Yan Z, Sonkusare S, Koval M, Isakson B. A venous-specific purinergic signaling cascade initiated by Pannexin 1 regulates TNFα-induced increases in endothelial permeability. Science Signaling 2021, 14 PMID: 33653920, PMCID: PMC8011850, DOI: 10.1126/scisignal.aba2940.Peer-Reviewed Original ResearchConceptsRNA expression profilingHydrolysis of ATPPannexin-1 channelsExpression profilingArterial endothelial cellsEndothelial cellsArterial endotheliumVenous endothelial cellsBarrier functionProtein analysisLung vascular permeabilityPannexin-1Claudin compositionBarrier function impairmentProinflammatory cytokine TNFαEndothelial cell barrierTargetable pathwaysMurine veinCecal ligationCell barrierFunction impairmentInflammatory insultLife spanDeficient miceVascular leakMineralocorticoid 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
Endothelial cell α-globin and its molecular chaperone α-hemoglobin–stabilizing protein regulate arteriolar contractility
Lechauve C, Butcher J, Freiwan A, Biwer L, Keith J, Good M, Ackerman H, Tillman H, Kiger L, Isakson B, Weiss M. Endothelial cell α-globin and its molecular chaperone α-hemoglobin–stabilizing protein regulate arteriolar contractility. Journal Of Clinical Investigation 2018, 128: 5073-5082. PMID: 30295646, PMCID: PMC6205378, DOI: 10.1172/jci99933.Peer-Reviewed Original Research