Statins, Mevalonate Pathway and its Intermediate Products in Placental Development and Preeclampsia

Author(s): Leonardo Ermini, Martin Post, Isabella Caniggia.

Journal Name: Current Molecular Pharmacology

Volume 10 , Issue 2 , 2017

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Abstract:

The mevalonate pathway synthesizes intermediates and products such as cholesterol and nonsterol isoprenoids that are crucial for cell survival and function. In the human placenta, the prenylation of proteins, rather than cholesterol synthesis, represents the main "metabolic target" of mevalonate metabolism. Major cellular functions depend on isoprenylation including proliferation, migration, metabolism and protein glycosylation that are all crucial for proper development of the embryo and the placenta. Statins are inhibitors of HMG-CoA reductase, the enzyme that catalyzes the reduction of HMG-CoA to mevalonic acid by NADPH. In vitro experiments using human placental explants suggest that statins elicit a detrimental effect on placental growth. However, animal and epidemiologic studies show no increase of fetal malformations after exposure to statins during pregnancy. Moreover, emerging evidence from mouse studies suggest that statins may be useful in preventing serious pregnancy complications like preeclampsia.

Keywords: Animal studies, mevalonate pathway, placental development, preeclampsia, pregnancy, statins.

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Article Details

VOLUME: 10
ISSUE: 2
Year: 2017
Page: [152 - 160]
Pages: 9
DOI: 10.2174/1874467209666160112123457
Price: $65

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