Endocannabinoid receptor blockade increases vascular endothelial growth factor and inflammatory markers in obese women with polycystic ovary syndrome

Javed, Zeeshan; Sathyapalan, Thozhukat; Atkin, Stephen L.; Coady, Anne-Marie; Kilpatrick, Eric S.

Abstract

© 2016 John Wiley & Sons Ltd Context: Animal studies suggest that cannabinoid receptor-1 (CB-1) blockade reduces inflammation and neovascularization by decreasing vascular endothelial growth factor (VEGF) levels associated with a reduction in inflammatory markers, thereby potentially reducing cardiovascular risk. Objective: To determine the impact of CB1 antagonism by rimonabant on VEGF and inflammatory markers in obese PCOS women. Design: Randomized, open-labelled parallel study. Setting: Endocrinology outpatient clinic in a referral centre. Subjects: Twenty patients with PCOS (PCOS) and biochemical hyperandrogenaemia with a body mass index of ≥30 kg/m 2 were recruited. Patients were randomized to 1·5 g daily of metformin or 20 mg daily of rimonabant. Main outcome measures: Post hoc review to detect VEGF and pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 before and after 12 weeks of treatment. Results: After 12 weeks of rimonabant treatment, there was a significant increase in VEGF (99·2 ± 17·6 vs 116·2 ± 15·8 pg/ml, P < 0·01) and IL-8 (7·4 ± 11·0 vs 18·1 ± 13·2 pg/ml, P < 0·05) but not after metformin (VEGF P = 0·7; IL-8 P = 0·9). There was no significant difference in the pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 following either treatment. Conclusion: This study suggests that rimonabant CB-I blockade paradoxically raised VEGF and the cytokine IL-8 in obese women with PCOS that may have offset the potential benefit associated with weight loss.

Citation

Javed, Z., Sathyapalan, T., Atkin, S. L., Coady, A.-M., & Kilpatrick, E. S. (2017). Endocannabinoid receptor blockade increases vascular endothelial growth factor and inflammatory markers in obese women with polycystic ovary syndrome. Clinical Endocrinology, 86(3), 384-387. https://doi.org/10.1111/cen.13239

• Acceptance Date: Sep 17, 2016
• Online Publication Date: Oct 7, 2016
• Publication Date: Mar 1, 2017
• Deposit Date: Sep 22, 2016
• Publicly Available Date: Oct 7, 2016
• Journal: Clinical endocrinology
• Print ISSN: 0300-0664
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 86
• Issue: 3
• Pages: 384-387
• DOI: https://doi.org/10.1111/cen.13239
• Keywords: CB-1 antagonism, Polycystic ovary syndrome
• Public URL: https://hull-repository.worktribe.com/output/443361
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1111/cen.13239/abstract
• Additional Information: Authors' accepted manuscript of article published in: Clinical endocrinology, 2017, v.86, issue 3
• Contract Date: Sep 22, 2016