Featured Publications
Endothelial 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 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
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
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-10Persistent change in cardiac fibroblast physiology after transient ACE inhibition
D'Souza K, Biwer L, Madhavpeddi L, Ramaiah P, Shahid W, Hale T. Persistent change in cardiac fibroblast physiology after transient ACE inhibition. AJP Heart And Circulatory Physiology 2015, 309: h1346-h1353. PMID: 26371174, DOI: 10.1152/ajpheart.00615.2015.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme InhibitorsAnimalsCardiomyopathiesCell ProliferationCells, CulturedChemokine CCL2Collagen Type IDisease Models, AnimalEnalaprilFibroblastsFibrosisGranulocyte-Macrophage Colony-Stimulating FactorHeart VentriclesHypertensionInflammation MediatorsMaleNG-Nitroarginine Methyl EsterNitric Oxide SynthasePhenotypeRats, Inbred SHRTime FactorsConceptsTransient ACE inhibitionACE inhibitionFibroblast physiologyArginine methyl ester treatmentCardiac fibroblastsAngiotensin-converting enzyme inhibitionPersistent changesMethyl ester treatmentChemoattractant protein-1Granulocyte macrophage-colony stimulating factorArginine methyl esterMacrophage-colony stimulating factorMacrophage-recruiting chemokinesCardiac fibroblast phenotypeRole of fibroblastsUntreated SHRHypertensive ratsNOS inhibitionWashout periodACE inhibitorsCardioprotective effectsChemokine releaseMyocardial injuryCardiac fibrosisNOS inhibitor
2012
Protection against L‐NAME‐induced reduction in cardiac output persists even after cessation of angiotensin‐converting enzyme inhibitor treatment
Biwer L, Broderick T, Xu H, Carroll C, Hale T. Protection against L‐NAME‐induced reduction in cardiac output persists even after cessation of angiotensin‐converting enzyme inhibitor treatment. Acta Physiologica 2012, 207: 156-165. PMID: 22834875, DOI: 10.1111/j.1748-1716.2012.02474.x.Peer-Reviewed Original ResearchConceptsL-NAMEMyocardial injuryCardiac functionEnalapril treatmentACE inhibitionCardiac outputL ratsL-NAME-induced reductionNitric oxide synthase inhibitorShort-term angiotensinTransient ACE inhibitionEnzyme inhibitor treatmentHeart failure treatmentCessation of treatmentOxide synthase inhibitorArginine methyl esterEosin-stained sectionsArterial pressureHypertensive ratsCardiac changesCardiac dysfunctionWashout periodCoronary flowMyocardial infarctionFailure treatment