Strong and positive association of Endothelin-1 with AGEs in PCOS: A causal relationship or a bystander?

OBJECTIVE: Advanced glycation end products (AGEs) activate the intracellular Nuclear Factor-kappa B pathway in endothelial cells, leading to production of endothelin-1 (ET-1), a peptide which causes endothelial dysfunction. The aim of the present study was to assess ET-1 and AGEs levels in women with polycystic ovary syndrome (PCOS) and controls and to investigate any potential relationship between them. DESIGN: Metabolic and hormonal data from 75 women with PCOS and 25 controls, matched for age and BMI were analyzed and correlated to AGEs and ET-1 levels. RESULTS: Serum levels of ET-1 (1.55 +/- 0.13 vs. 0.37 +/- 0.10 pmol/l, p:0.003) and AGEs (8.34 +/- 1,81 vs. 5.77 +/- 0.78U/ml, p:0.002) were significantly higher in the PCOS group. ET-1 was correlated with AGES (r:0.54, p < 0.001), Testosterone (r:0.38, p < 0.001), Delta A4 (r:0.41, p < 0.001) and FAI (r:0.21, p < 0.05). However, multiple linear regression analysis in the total study population showed that ET-1 was positively associated only with AGES (beta:0.22, p < 0.001). CONCLUSIONS: ET-1 levels were positively and strongly associated with AGEs in both PCOS women and controls, suggesting that the detrimental effect of AGEs on endothelial cells may involve increased ET-1 production.