P81 Antibody to Cardiotonic Steroid Reduces Blood Pressure and Vascular Fibrosis in Preeclampsia
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Background: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). We demonstrated that MBG induces fibrosis via mechanism involving inhibition of Fli1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis.
Objectives and Methods: We hypothesized that PE blockade of increased MBG with antibody would lessen the fibrosis of umbilical arteries and lower the blood pressure in rats with PE. We tested 36 pregnant Sprague-Dawley rats in which 12 were made hypertensive by 1.8% Na supplementation (days 6–19 of gestation), 12 pregnant rats served controls. At day 19, PE rats received one intraperitoneal injection of polyclonal anti-MBG-4 antibody (0.5 ug/mL) for 4 hours.
Results: PE was associated with higher blood pressure (117 ± 2 vs 107 ± 2 mmHg; p < 0.01), plasma MBG levels (1.54 ± 0.34 vs 0.49 ± 0.11 nmol/L; p < 0.01), protein excretion (26 vs 12 mg/24 hours), sFlt-1 (4-fold), decrease in Fli1 (7-fold) and increase in collagen-1 in aorta (4-fold) vs. control rats (all p < 0.01). In 12 rats was treated with polyclonal anti-MBG-4 antibody blood pressure dropped (93 ± 3 mmHg) and Fli1 was decreased much less (2-fold; p < 0.01 vs nontreated rats).
Conclusion: These results demonstrate that in experimental PE elevated MBG level is implicated in umbilical fibrosis via suppression of Fli1. Supported by Russian Scientific Foundation grant № 18-15-00222.
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Cite this article
TY - JOUR AU - NI Agalakova AU - VA Reznik AU - OV Nadei AU - IA Ershov AU - OS Rassokha AU - ML Vasyutina AU - MM Galagudza AU - AY Bagrov PY - 2020 DA - 2020/02/17 TI - P81 Antibody to Cardiotonic Steroid Reduces Blood Pressure and Vascular Fibrosis in Preeclampsia JO - Artery Research SP - S124 EP - S124 VL - 25 IS - Supplement 1 SN - 1876-4401 UR - https://doi.org/10.2991/artres.k.191224.111 DO - 10.2991/artres.k.191224.111 ID - Agalakova2020 ER -