title: Statins, Mevalonate Pathway and its Intermediate Products in Placental Development and Preeclampsia.
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.
authors.affiliation: Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Ermini
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Post
authors.affiliation: Isabella Caniggia, Mount Sinai Hospital, The Lunenfeld-Tanenbaum Research Institute, 25 Orde Street, Room 6-1004-3, Toronto, Ontario, Canada.
authors.forename: Isabella
authors.initials: I
authors.lastname: Caniggia
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008798:Mevalonic Acid / Q000378:metabolism*; D051379:Mice; D010929:Placentation / Q000187:drug effects*; D011225:Pre-Eclampsia / Q000378:metabolism / Q000517:prevention & control*; D011247:Pregnancy; D054876:Prenylation; D013729:Terpenes / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013729:Terpenes; D008798:Mevalonic Acid
keywords: Animal studies; mevalonate pathway; placental development; preeclampsia; pregnancy; statins