Title:Statins, Mevalonate Pathway and its Intermediate Products in Placental Development and Preeclampsia
Volume: 10
Author(s): Leonardo Ermini, Martin Post and Isabella Caniggia
Affiliation:
Keywords:
Animal studies, mevalonate pathway, placental development, preeclampsia, pregnancy, statins.
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.
