Endogenous Secretory RAGE in Obese Women: Association with Platelet Activation and Oxidative Stress

• Published in: The journal of clinical endocrinology and metabolism 2012-09, Vol.97 (9), p.E1726-E1730
• Main Authors: Vazzana, Natale, Guagnano, Maria Teresa, Cuccurullo, Chiara, Ferrante, Elisabetta, Lattanzio, Stefano, Liani, Rossella, Romano, Mario, Davì, Giovanni
• Format: Article
• Language: English
• Subjects: Adiponectin - blood; Adult; Anthropometry; Blood Glucose - metabolism; Blood Pressure - physiology; Cardiovascular Diseases - epidemiology; Dinoprost - analogs & derivatives; Dinoprost - urine; Female; Humans; Linear Models; Lipid Peroxidation - physiology; Lipids - blood; Middle Aged; Obesity - blood; Obesity - metabolism; Oxidative Stress - physiology; Platelet Activation - physiology; Receptor for Advanced Glycation End Products; Receptors, Immunologic - blood; Receptors, Immunologic - metabolism; Risk; Thromboxane B2 - analogs & derivatives; Thromboxane B2 - urine; Weight Loss - physiology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2012-1473

Context: The receptor for advanced glycation end-products (RAGE) has been implicated in obesity-related metabolic disease and accelerated atherothrombosis. Objective: We tested the hypothesis that changes in endogenous secretory (es)RAGE levels as a result of excess adiposity and oxidative stress may contribute to enhancing platelet activation in obese women, thus increasing the cardiovascular risk. Patients: Eighty otherwise healthy obese women and 20 nonobese women were studied. Results: esRAGE and plasma adiponectin were reduced in obese women [median (interquartile range), 0.18 (0.13–0.26) vs. 0.38 (0.20–0.48) ng/ml, P = 0.003; and 4.4 (2.8–6.4) vs. 10.0 (6.9–12.5) μg/ml, P < 0.0001, respectively] who also displayed higher urinary 11-dehydro-thromboxane B2 (11-dehydro-TXB2) [795 (572–1089) vs. 211 (135–301) pg/mg creatinine; P < 0.0001] and 8-iso-prostaglandin F2α (8-iso-PGF2α) [544 (402–698) vs. 149 (98–219) pg/mg creatinine; P < 0.0001] compared to nonobese women. Direct correlations between plasma adiponectin and esRAGE (Rho = 0.43; P < 0.0001) and between urinary 8-iso-PGF2α and 11-dehydro-TXB2 (Rho = 0.36; P = 0.001) were observed in obese women. Moreover, plasma esRAGE and urinary 11-dehdro-TXB2 were inversely related (Rho = −0.29; P = 0.008). On multiple linear regression analysis, urinary 8-iso-PGF2α and plasma esRAGE were independent predictors of urinary 11-dehydro-TXB2. In five obese women, a short-term weight loss program gave a significant increase in esRAGE and decrease in urinary 8-iso-PGF2α and 11-dehydro-TXB2. Conclusion: In otherwise healthy obese women, low plasma esRAGE levels are associated with reduced circulating adiponectin and enhanced thromboxane biosynthesis, which is in part mediated by increased lipid peroxidation. Thus, excess adiposity may be implicated in RAGE hyperactivation and thromboxane-dependent platelet activation, contributing to obesity-related metabolic and vascular disease.