Internal Medicine and Center of Excellence on Aging, Gabriele d'Annunzio University of Chieti, 66013 Chieti, Italy.
J Clin Endocrinol Metab. 2012 Sep;97(9):E1726-30. doi: 10.1210/jc.2012-1473. Epub 2012 Jul 3.
The receptor for advanced glycation end-products (RAGE) has been implicated in obesity-related metabolic disease and accelerated atherothrombosis.
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.
Eighty otherwise healthy obese women and 20 nonobese women were studied.
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 B(2) (11-dehydro-TXB(2)) [795 (572-1089) vs. 211 (135-301) pg/mg creatinine; P < 0.0001] and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)) [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-PGF(2α) and 11-dehydro-TXB(2) (Rho = 0.36; P = 0.001) were observed in obese women. Moreover, plasma esRAGE and urinary 11-dehdro-TXB(2) were inversely related (Rho = -0.29; P = 0.008). On multiple linear regression analysis, urinary 8-iso-PGF(2α) and plasma esRAGE were independent predictors of urinary 11-dehydro-TXB(2). In five obese women, a short-term weight loss program gave a significant increase in esRAGE and decrease in urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2).
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.
晚期糖基化终产物（RAGE）受体已被牵连到肥胖相关的代谢疾病和加速动脉粥样硬化血栓形成。
我们检验了这样一个假说，即多余的肥胖和氧化应激导致的内源性分泌型 RAGE（esRAGE）水平的改变可能会促进肥胖女性血小板的激活，从而增加心血管风险。
80 名其他方面健康的肥胖女性和 20 名非肥胖女性被纳入研究。
肥胖女性的 esRAGE 和血浆脂联素水平降低[中位数（四分位距），0.18（0.13-0.26）vs. 0.38（0.20-0.48）ng/ml，P=0.003；4.4（2.8-6.4）vs. 10.0（6.9-12.5）μg/ml，P＜0.0001]，并且她们的尿液 11-脱氢血栓烷 B2（11-dehydro-TXB2）[795（572-1089）vs. 211（135-301）pg/mg 肌酐；P＜0.0001]和 8-异前列腺素 F2α（8-iso-PGF2α）[544（402-698）vs. 149（98-219）pg/mg 肌酐；P＜0.0001]水平也较高。与非肥胖女性相比，肥胖女性的血浆脂联素与 esRAGE 呈直接正相关（Rho=0.43；P＜0.0001），尿液 8-iso-PGF2α 与 11-dehydro-TXB2 呈直接正相关（Rho=0.36；P=0.001）。此外，血浆 esRAGE 与尿液 11-脱氢血栓烷 B2 呈负相关（Rho=-0.29；P=0.008）。多元线性回归分析显示，尿液 8-iso-PGF2α 和血浆 esRAGE 是尿液 11-dehydro-TXB2 的独立预测因子。在 5 名肥胖女性中，短期减重计划显著增加了 esRAGE 水平，降低了尿液 8-iso-PGF2α 和 11-dehydro-TXB2 的水平。
在其他方面健康的肥胖女性中，低血浆 esRAGE 水平与循环脂联素减少和血栓烷生物合成增加有关，这部分是由脂质过氧化增加介导的。因此，多余的肥胖可能与 RAGE 的过度激活和血栓烷依赖性血小板激活有关，从而导致肥胖相关的代谢和血管疾病。
