title: Statins inhibit monocyte chemotactic protein 1 expression in endometriosis.
abstract: Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future.
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Hakan
authors.initials: H
authors.lastname: Cakmak
authors.forename: Murat
authors.initials: M
authors.lastname: Basar
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Seval-Celik
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Osteen
authors.forename: Antoni J
authors.initials: AJ
authors.lastname: Duleba
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
authors.forename: Aydin
authors.initials: A
authors.lastname: Arici
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D004195:Disease Models, Animal; D004715:Endometriosis / Q000378:metabolism*; D004717:Endometrium / Q000637:transplantation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D019821:Simvastatin / Q000494:pharmacology; D014183:Transplantation, Heterologous
chemical_list: D018932:Chemokine CCL2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D019821:Simvastatin