Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

Çakmak, Hakan; Başar, Murat; Seval-Celik, Yasemin; Osteen, Kevin G.; Dulęba, Antoni J.; Taylor, Hugh S.; Lockwood, Charles J.; Arıcı, Aydın

doi:10.1177/1933719111430998

Cited by 33 publications

(34 citation statements)

References 42 publications

(83 reference statements)

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“…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).…”

Section: Discussionmentioning

confidence: 98%

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

Dworacka

Krzyżagórska²,

Wesołowska

et al. 2014

European Journal of Pharmacology

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Section: Discussionmentioning

confidence: 98%

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

Dworacka

Krzyżagórska²,

Wesołowska

et al. 2014

European Journal of Pharmacology

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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BackgroundSimvastatin is a promising new drug for the treatment of endometriosis. It is a cholesterol-lowering drug that acts by inhibiting HMG-CoA reductase, resulting in a decrease in mevalonate, a precursor of cholesterol and monocyte chemoattractant protein-1 (MCP-1). This study investigated the effect of pre-operative oral simvastatin administration on MCP-1 gene expression and serum MCP-1 protein levels in patients with endometriosis.MethodsA prospective, randomized, controlled study was conducted at the Reproductive Endocrinology Unit of the Department of Obstetrics and Gynecology at the Faculty of Medicine Ramathibodi Hospital. Forty women (mean age: 18–45 years) scheduled for laparoscopic surgery who had been diagnosed with endometriosis were recruited and randomly assigned to either a treatment group (20 mg/d of orally administered simvastatin for 2 weeks before surgery) or an untreated control group. Serum was collected before and after treatment and protein levels of MCP-1 were determined. MCP-1 and CD68 transcript levels were also quantified using real-time PCR on endometriotic cyst tissues.Results MCP-1 gene expression on endometriotic cyst was not significantly different between the simvastatin-treated and untreated groups (P = 0.99). CD68 expression was higher in the treatment group compared to the control group, but this was not statistically significant (P = 0.055). Serum MCP-1 levels following simvastatin treatment were higher than in samples obtained before treatment (297.89 ± 70.77 and 255.51 ± 63.79 pg/ml, respectively) (P = 0.01).ConclusionsTreatment with 20 mg/d of simvastatin for 2 weeks did not reduce the expression of either the chemokine MCP-1 gene or macrophage-specific genes. Cumulatively, this suggests that simvastatin is not ideal for treating endometriosis because a higher dose of simvastatin (40–100 mg/d) would be needed to achieve the target outcome, which would significantly increase the risk of myopathy in patients.Trial registrationThai Clinical Trials Registry TCTR20130627003 Registered: June 27, 2013.

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“…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.…”

Section: Statinsmentioning

confidence: 98%