1. Antibody against Na/K-ATPase Inhibitor Lowers Blood Pressure and Increases Vascular Fli1 in Experimental Preeclampsia.
- Author
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Agalakova NI, Reznik VA, Nadei OV, Ershov IA, Rassokha OS, Vasyutina ML, Ivanov DO, Adair CD, Galagudza MM, and Bagrov AY
- Subjects
- Animals, Bufanolides metabolism, Disease Models, Animal, Female, Fibrosis, Pre-Eclampsia enzymology, Pre-Eclampsia pathology, Pre-Eclampsia physiopathology, Pregnancy, Rats, Sprague-Dawley, Sodium Chloride, Dietary, Umbilical Arteries enzymology, Umbilical Arteries pathology, Umbilical Arteries physiopathology, Up-Regulation, Antibodies pharmacology, Antihypertensive Agents pharmacology, Blood Pressure drug effects, Bufanolides antagonists & inhibitors, Pre-Eclampsia prevention & control, Proto-Oncogene Protein c-fli-1 metabolism, Sodium-Potassium-Exchanging ATPase metabolism, Umbilical Arteries drug effects
- Abstract
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. 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., Methods: 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 mm Hg; 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 (3-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 treated with polyclonal anti-MBG-4 antibody blood pressure dropped (93 ± 3 mm Hg) and Fli1 was decreased much less (2-fold; P < 0.01 vs. nontreated rats)., Conclusions: These results demonstrate that in experimental PE elevated MBG level is implicated in umbilical fibrosis via suppression of Fli1., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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