Agalakova, N.I.; Kolodkin, N.I.; Adair, C.D.; Trashkov, A.P.; Bagrov, A.Y. Preeclampsia: Сardiotonic Steroids, Fibrosis, Fli1 and Hint to Carcinogenesis. Int. J. Mol. Sci.2021, 22, 1941.
Agalakova, N.I.; Kolodkin, N.I.; Adair, C.D.; Trashkov, A.P.; Bagrov, A.Y. Preeclampsia: Сardiotonic Steroids, Fibrosis, Fli1 and Hint to Carcinogenesis. Int. J. Mol. Sci. 2021, 22, 1941.
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 which 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 deposition of collagen in the vascular tissues and altered vascular functions. Moreover, in vitro and in vivo neutralization of marinobufagenin is associated with restoration of Fli1. The inverse relationship between marinobufagenin and Fli1 opens new possibilities in the treatment of cancer: since Fli1 is a proto-oncogene, a hypothesis on suppression of Fli1 by cardiotonic steroids as potential anti-tumor therapeutic strategy is discussed as well. We propose a novel therapy of preeclampsia which is based on immunoneutralization of the marinobufagenin by monoclonal antibodies, which is capable to impair marinobufagenin-Na/K-ATPase interactions.
Preeclampsia; Na/K-ATPase; marinobufagenin; Fli1
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