P81 Antibody to Cardiotonic Steroid Reduces Blood Pressure and Vascular Fibrosis in Preeclampsia

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.

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.