Abstract
Despite prophylaxis and attempts to select a therapy, the frequency of preeclampsia does not decrease and it still takes the leading position in the structure of maternal mortality and morbidity worldwide. In this review, we present a new theory of the etiology and pathogenesis of preeclampsia that is based on the interaction of Na/K-ATPase and its endogenous ligands including marinobufagenin. The signaling pathway of marinobufagenin involves an inhibition of transcriptional factor Fli1, a negative regulator of collagen synthesis, followed by the deposition of collagen in the vascular tissues and altered vascular functions. Moreover, in vitro and in vivo neutralization of marinobufagenin is associated with the restoration of Fli1. The inverse relationship between marinobufagenin and Fli1 opens new possibilities in the treatment of cancer; as Fli1 is a proto-oncogene, a hypothesis on the suppression of Fli1 by cardiotonic steroids as a potential anti-tumor therapeutic strategy is discussed as well. We propose a novel therapy of preeclampsia that is based on immunoneutralization of the marinobufagenin by monoclonal antibodies, which is capable of impairing marinobufagenin-Na/K-ATPase interactions.
Highlights
Preeclampsia (PE) is one of the most common hypertensive disorders developing during pregnancy [1]
This model postulates that one of the major causes of PE is linked with an enhanced synthesis of cardiotonic steroids (CS), which leads to disturbances in intracellular signaling and to altered vascular reactivity including arterial fibrosis
The direct link between cancerogenesis, MBG and the activity of Fli1 is yet to be established. It appears that the introduction of antibodies to MBG eliminated the inhibition of Na/K-ATPase in red blood cells obtained from the blood of patients with PE ex vivo [27,28]
Summary
Preeclampsia (PE) is one of the most common hypertensive disorders developing during pregnancy [1]. Despite the ongoing prophylaxis and repeated attempts to select a therapy, it is still not possible to reduce the incidence of PE. As a result, it is one of the leading causes of maternal and perinatal morbidity and mortality. The present review is focused on the mechanisms related to the abnormal processes in blood vessels and presents the “fibrotic” concept of PE development This model postulates that one of the major causes of PE is linked with an enhanced synthesis of cardiotonic steroids (CS), which leads to disturbances in intracellular signaling and to altered vascular reactivity including arterial fibrosis. The immunoneutralization of CS as a valuable approach to relieve the symptoms of PE and a promising therapy are discussed as well
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