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4.8 Placental Na/K-Atpase Inhibitor Marinobufagenin Induces Arterial Wall Fibrosis in Preeclampsia
Artery Research volume 24, pages 77–78 (2018)
Abstract
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 fivefold 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.
References
Supported in part by the National Institute on Aging, NIH and by Russian Scientific Foundation grant No 18-15-00222.
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This is an open access article distributed under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
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Fedorova, O., Aglakova, N., Grigorova, Y. et al. 4.8 Placental Na/K-Atpase Inhibitor Marinobufagenin Induces Arterial Wall Fibrosis in Preeclampsia. Artery Res 24, 77–78 (2018). https://doi.org/10.1016/j.artres.2018.10.047
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DOI: https://doi.org/10.1016/j.artres.2018.10.047