2023
Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Zhao S, Mekbib K, van der Ent M, Allington G, Prendergast A, Chau J, Smith H, Shohfi J, Ocken J, Duran D, Furey C, Hao L, Duy P, Reeves B, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu P, Wang Y, Mane S, Piwowarczyk P, Fehnel K, See A, Iskandar B, Aagaard-Kienitz B, Moyer Q, Dennis E, Kiziltug E, Kundishora A, DeSpenza T, Greenberg A, Kidanemariam S, Hale A, Johnston J, Jackson E, Storm P, Lang S, Butler W, Carter B, Chapman P, Stapleton C, Patel A, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay E, Zhao H, Moreno-De-Luca A, Proctor M, Smith E, Orbach D, Alper S, Nicoli S, Boggon T, Lifton R, Gunel M, King P, Jin S, Kahle K. Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Nature Communications 2023, 14: 7452. PMID: 37978175, PMCID: PMC10656524, DOI: 10.1038/s41467-023-43062-z.Peer-Reviewed Original ResearchConceptsEphrin receptor B4Galen malformationBrain arteriovenous malformationsP120 RasGAPTransmitted variantsArteriovenous malformationsDe novo variantsSingle-cell transcriptomesSignificant burdenCerebrovascular developmentIntegrative genomic analysisEndothelial cellsVenous networkAdditional probandsMalformationsNovo variantsMissense variantsGenomic analysisDevelopmental angiogenesisVascular developmentDamaging variantsVeinRasGAPIntegrated analysisPatientsIsradipine therapy in Cacna1dIle772Met/+ mice ameliorates primary aldosteronism and neurologic abnormalities
Stölting G, Dinh H, Volkert M, Hellmig N, Schewe J, Hennicke L, Seidel E, Oberacher H, Zhang J, Lifton R, Urban I, Long M, Rivalan M, Nottoli T, Scholl U. Isradipine therapy in Cacna1dIle772Met/+ mice ameliorates primary aldosteronism and neurologic abnormalities. JCI Insight 2023, 8: e162468. PMID: 37698934, PMCID: PMC10619505, DOI: 10.1172/jci.insight.162468.Peer-Reviewed Original ResearchConceptsPrimary aldosteronismNeurologic abnormalitiesZona glomerulosaIntracellular calciumElevated aldosterone/renin ratioCalcium channel blocker isradipineAldosterone/renin ratioL-type calcium channel Cav1.3Aldosterone-producing lesionsAdrenal aldosterone-producing adenomaHigh-salt dietTonic-clonic seizuresChannel blocker isradipineReduced body weightAldosterone-producing adenomaTherapy of patientsElevated intracellular calciumFunction mutationsDe novo germline mutationsDays of ageIsradipine therapyAldosterone levelsRenin ratioSerum aldosteroneRotarod test
2021
Enhanced Ca2+ signaling, mild primary aldosteronism, and hypertension in a familial hyperaldosteronism mouse model (Cacna1hM1560V/+)
Seidel E, Schewe J, Zhang J, Dinh HA, Forslund SK, Markó L, Hellmig N, Peters J, Muller DN, Lifton RP, Nottoli T, Stölting G, Scholl UI. Enhanced Ca2+ signaling, mild primary aldosteronism, and hypertension in a familial hyperaldosteronism mouse model (Cacna1hM1560V/+). Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2014876118. PMID: 33879608, PMCID: PMC8092574, DOI: 10.1073/pnas.2014876118.Peer-Reviewed Original ResearchConceptsMild primary aldosteronismHigh-salt dietPrimary aldosteronismAldosterone productionNormal aldosterone productionPeak intracellular calcium concentrationRenin-angiotensin systemSystolic blood pressureEarly-onset hypertensionAdrenal glomerulosa cellsIntracellular calcium concentrationWild-type littermatesElevated intracellular CaCalcium entry pathwayCorresponding knockout miceFunction mutationsFH-IVPlasma aldosteroneRenin ratioBlood pressureChronic settingAdrenal morphologyZona glomerulosaGlomerulosa cellsAdrenal slices