Marinobufagenin as a therapeutic target

National Institute On Aging

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Abstract

Methods and Results: Eleven patients with PE (mean BP 124+/-4 mmHg; age 29+/-2 years; 39 weeks gest. age) and 10 gestational age-matched normal pregnant subjects (mean BP 92+/-2 mmHg; controls) were enrolled in the clinical study. PE was associated with a higher placental (0.04+/-0.01 vs. 0.49+/-0.11 pmol/g tissue; p < 0.01) and plasma MBG (0.5+/-0.1 vs. 1.6+/-0.5 nmol/L; p < 0.01), lower Na/K-ATPase activity in erythrocytes (2.7+/-0.2 vs. 1.5+/-0.2 umol Pi/mL/hr; p < 0.01), 9-fold decrease of Fli-1 level and 2.5-fold increase of collagen-1 in placentae (p < 0.01) vs. control. Incubation of umbilical arteries from control patients with 1 nmol/L MBG was associated with four-fold decrease in Fli-1 level and two-fold increase in collagen-1 level vs. those incubated with placebo (p < 0.01), i.e., physiological concentration of MBG mimicked effect of PE in vitro. Collagen-1 abundance in umbilical arteries from PE patients was 4-fold higher than in control arteries, and this PE-associated fibrosis was reversed by monoclonal anti-MBG antibody ex vivo. Conclusion: These results demonstrate that elevated placental MBG level is implicated in the development of fibrosis of the placenta and umbilical arteries in PE, and represent a potential therapeutic target.