4.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIA
| Autor: | Vitalily Reznik, Alexei Y. Bagrov, Valintina Zernetkina, Olga V. Fedorova, Natalia Aglakova, Yulia Grigorova, Edward G. Lakatta, Wen Wei |
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| Rok vydání: | 2018 |
| Předmět: |
lcsh:Diseases of the circulatory (Cardiovascular) system
medicine.medical_specialty Marinobufagenin lcsh:Specialties of internal medicine business.industry General Medicine medicine.disease Na-K ATPase inhibitor Preeclampsia chemistry.chemical_compound Endocrinology chemistry lcsh:RC581-951 lcsh:RC666-701 Fibrosis Internal medicine medicine Arterial wall business |
| Zdroj: | Artery Research, Vol 24 (2018) |
| ISSN: | 1876-4401 |
| DOI: | 10.1016/j.artres.2018.10.047 |
| Popis: | Background: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Immunoneutralization of heightened MBG by Digibind, a digoxin antibody, reduces blood pressure (BP) in patients with PE, and anti-MBG monoclonal antibody lessens BP in a rat model of PE. Recently, we demonstrated that MBG induces fibrosis in cardiovascular tissues via mechanism involving inhibition of Fli1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis. Objectives and Methods: We hypothesized that in PE, elevated placental MBG levels is associated with development of fibrosis of umbilical arteries. Thirty patients with PE (mean BP = 118 ± 4 mmHg; 29 ± 2 years; 35 weeks gest. age) and 26 gestational age-matched normal pregnant subjects (mean BP = 92 ± 2 mmHg; controls) were enrolled in the clinical study. Results: PE was associated with a higher placental MBG level (48.6 ± 7.0 vs. 13.6 ± 2.5 nmol/g; P < .01), four-fold decrease of Fli1 and two-fold increase of collagen-1 in placentae (P < .01) vs. control. PE was associated with five-fold decrease in Fli1 level and two-fold increase in collagen-1 level in the PE umbilical arteries vs. those from the normal subjects (P < .01). Isolated rings of umbilical arteries from the subjects with PE exhibited impaired response to the relaxant effect of sodium nitroprusside, vs. control vessels (EC50 = 141 nmol/L vs. EC50 = 0.9 nmol/L; P < .001). In vitro 10 nmol MBG mimicked effect of PE, and monoclonal anti-MBG antibody reversed this effect. Conclusion: These results demonstrate that elevated placental MBG level is implicated in the development of fibrosis umbilical arteries in PE. |
| Databáze: | OpenAIRE |
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