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

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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/m2 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.

Original languageEnglish
Pages (from-to)384-387
Number of pages4
JournalClinical Endocrinology
Volume86
Issue number3
DOIs
Publication statusPublished - 1 Mar 2017
Externally publishedYes

Fingerprint

rimonabant
Endocannabinoids
Polycystic Ovary Syndrome
Vascular Endothelial Growth Factor A
Interleukin-8
Interleukin 1 Receptor Antagonist Protein
Metformin
Cytokines
Interleukin-1
Interleukin-10
Interleukin-2
Interleukin-6
Cannabinoid Receptors
Endocrinology
Ambulatory Care Facilities
Weight Loss
Body Mass Index
Therapeutics
Referral and Consultation
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Endocannabinoid receptor blockade increases vascular endothelial growth factor and inflammatory markers in obese women with polycystic ovary syndrome. / Sathyapalan, Thozhukat; Javed, Zeeshan; Kilpatrick, Eric S.; Coady, Anne Marie; Atkin, Stephen.

In: Clinical Endocrinology, Vol. 86, No. 3, 01.03.2017, p. 384-387.

Research output: Contribution to journalArticle

Sathyapalan, Thozhukat ; Javed, Zeeshan ; Kilpatrick, Eric S. ; Coady, Anne Marie ; Atkin, Stephen. / Endocannabinoid receptor blockade increases vascular endothelial growth factor and inflammatory markers in obese women with polycystic ovary syndrome. In: Clinical Endocrinology. 2017 ; Vol. 86, No. 3. pp. 384-387.
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abstract = "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/m2 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.",
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N2 - 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/m2 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.

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