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.

Circulating monocyte chemotactic protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1) and angiogenin in type 2 diabetic patients treated with statins in low doses

“…The revealed data based on experimental research show that statins have the potential to both inhibit and promote neovascularization (Asai et al, 2012;Cakmak et al, 2012;Hu et al, 2008;Massaro et al, 2010). It was proposed that statins have a proangiogenic effect at low concentrations (nanomolar), whereas higher concentrations (micromolar) decrease angiogenesis (Urbich et al, 2002;Weis et al, 2002).…”

Effect of simvastatin on monocyte chemoattractant protein-1 expression in endometriosis patients: a randomized controlled trial

“…They demonstrated a potent inhibitory effect of simvastatin on the development of endometriosis and on matrix metalloproteinase-3 (MMP-3) [ 10 ]. Cakmak et al investigated the effects of simvastatin (5 and 25 mg/kg/d for 10 d) in a nude mouse model of endometriosis, and observed a significant decrease in MCP-1 production [ 27 ]. However, no studies have reported the effect of simvastatin on endometriosis in humans.…”

Pharmacologic therapies in endometriosis: a systematic review

“…The anti-inflammatory properties of simvastatin and mevastatin have been demonstrated by both in vitro culture of endometrial cells and endometriosis induced in mice (31). In both models, monocyte chemotactic protein-1 (MCP-1) expression was inhibited by these drugs in a dose-dependent fashion.…”