دورية أكاديمية
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Mitochondrial-targeted antioxidant attenuates preeclampsia-like phenotypes induced by syncytiotrophoblast-specific Gαq signaling.

التفاصيل البيبلوغرافية
العنوان: Mitochondrial-targeted antioxidant attenuates preeclampsia-like phenotypes induced by syncytiotrophoblast-specific Gαq signaling.
المؤلفون: Opichka MA; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA., Livergood MC; Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, USA., Balapattabi K; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA., Ritter ML; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA., Brozoski DT; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA., Wackman KK; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA., Lu KT; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA., Kozak KN; Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, USA., Wells C; Electron Microscopy Core Facility, Medical College of Wisconsin, Milwaukee, USA., Fogo AB; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, USA., Gibson-Corley KN; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, USA., Kwitek AE; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, USA.; Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, USA., Sigmund CD; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, USA.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, USA., McIntosh JJ; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA.; Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, USA.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, USA., Grobe JL; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, USA.; Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, USA.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, USA.; Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, USA.
المصدر: Science advances [Sci Adv] 2023 Dec; Vol. 9 (48), pp. eadg8118. Date of Electronic Publication: 2023 Dec 01.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
مواضيع طبية MeSH: Pre-Eclampsia*, Animals ; Mice ; Pregnancy ; Female ; Humans ; Trophoblasts ; Placenta ; Antioxidants/pharmacology ; GTP-Binding Proteins ; Proteinuria
مستخلص: Syncytiotrophoblast stress is theorized to drive development of preeclampsia, but its molecular causes and consequences remain largely undefined. Multiple hormones implicated in preeclampsia signal via the Gαq cascade, leading to the hypothesis that excess Gαq signaling within the syncytiotrophoblast may contribute. First, we present data supporting increased Gαq signaling and antioxidant responses within villous and syncytiotrophoblast samples of human preeclamptic placenta. Second, Gαq was activated in mouse placenta using Cre-lox and DREADD methodologies. Syncytiotrophoblast-restricted Gαq activation caused hypertension, kidney damage, proteinuria, elevated circulating proinflammatory factors, decreased placental vascularization, diminished spiral artery diameter, and augmented responses to mitochondrial-derived superoxide. Administration of the mitochondrial-targeted antioxidant Mitoquinone attenuated maternal proteinuria, lowered circulating inflammatory and anti-angiogenic mediators, and maintained placental vascularization. These data demonstrate a causal relationship between syncytiotrophoblast stress and the development of preeclampsia and identify elevated Gαq signaling and mitochondrial reactive oxygen species as a cause of this stress.
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معلومات مُعتمدة: T32 HL007852 United States HL NHLBI NIH HHS; R01 HL134850 United States HL NHLBI NIH HHS; K08 HL150340 United States HL NHLBI NIH HHS; P01 HL084207 United States HL NHLBI NIH HHS; UL1 TR001436 United States TR NCATS NIH HHS; R01 DK056942 United States DK NIDDK NIH HHS; R01 DK133121 United States DK NIDDK NIH HHS
المشرفين على المادة: 0 (Antioxidants)
EC 3.6.1.- (GTP-Binding Proteins)
تواريخ الأحداث: Date Created: 20231201 Date Completed: 20231204 Latest Revision: 20231213
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10691776
DOI: 10.1126/sciadv.adg8118
PMID: 38039359
قاعدة البيانات: MEDLINE
الوصف
تدمد:2375-2548
DOI:10.1126/sciadv.adg8118