Artery Research

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Volume 24, Issue C, December 2018, Pages 77 - 78

4.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIA

Authors
Olga Fedorova1, Natalia Aglakova2, Yulia Grigorova3, Vitalily Reznik4, Valintina Zernetkina3, Wen Wei3, Edward Lakatta3, Alexei Bagrov5
1National Institute on Aging, NIH, Baltimore, MD, USA
2Sechenov Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia
3Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, MD, USA
4Department of Obstetrics and Gynecology, School of Pediatric Medicine, St. Petersburg, Russia
5Sechenov Institute of Evolutionary Physiology, St. Petersburg, Russia
Available Online 4 December 2018.
DOI
10.1016/j.artres.2018.10.047How to use a DOI?
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 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.

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This is an open access article distributed under the CC BY-NC license.

Reference

1. Supported in part by the National Institute on Aging, NIH and by Russian Scientific Foundation grant No 18-15-00222.
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Journal
Artery Research
Volume-Issue
24 - C
Pages
77 - 78
Publication Date
2018/12/04
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.1016/j.artres.2018.10.047How to use a DOI?
Open Access
This is an open access article distributed under the CC BY-NC license.

Cite this article

risenwbib
TY  - JOUR
AU  - Olga Fedorova
AU  - Natalia Aglakova
AU  - Yulia Grigorova
AU  - Vitalily Reznik
AU  - Valintina Zernetkina
AU  - Wen Wei
AU  - Edward Lakatta
AU  - Alexei Bagrov
PY  - 2018
DA  - 2018/12/04
TI  - 4.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIA
JO  - Artery Research
SP  - 77
EP  - 78
VL  - 24
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2018.10.047
DO  - 10.1016/j.artres.2018.10.047
ID  - Fedorova2018
ER  -