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 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). 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.
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 obesewomen, thus increasing the cardiovascular risk. PATIENTS: Eighty otherwise healthy obesewomen and 20 nonobese women were studied. RESULTS: esRAGE and plasma adiponectin were reduced in obesewomen [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 obesewomen. 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 obesewomen, 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). CONCLUSION: In otherwise healthy obesewomen, 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.
Authors: Liang Chen; Zhigang Duan; Lesley Tinker; Haleh Sangi-Haghpeykar; Howard Strickler; Gloria Y F Ho; Marc J Gunter; Thomas Rohan; Craig Logsdon; Donna L White; Kathryn Royse; Hashem B El-Serag; Li Jiao Journal: Cancer Epidemiol Date: 2016-04-18 Impact factor: 2.984
Authors: Michelle M Pacis; Chelsea N Fortin; Shvetha M Zarek; Sunni L Mumford; James H Segars Journal: J Assist Reprod Genet Date: 2014-12-30 Impact factor: 3.412
Authors: Elena De Marchi; Federica Baldassari; Angela Bononi; Mariusz R Wieckowski; Paolo Pinton Journal: Oxid Med Cell Longev Date: 2013-03-27 Impact factor: 6.543
Authors: Claire K Inman; Abdullah Aljunaibi; Hyunwook Koh; Abdishakur Abdulle; Raghib Ali; Abdullah Alnaeemi; Eiman Al Zaabi; Naima Oumeziane; Marina Al Bastaki; Mohammed Al-Houqani; Fatma Al-Maskari; Ayesha Al Dhaheri; Syed M Shah; Laila Abdel Wareth; Wael Al Mahmeed; Habiba Alsafar; Fatme Al Anouti; Ayesha Al Hosani; Muna Haji; Divya Galani; Matthew J O'Connor; Jiyoung Ahn; Tomas Kirchhoff; Scott Sherman; Richard B Hayes; Huilin Li; Ravichandran Ramasamy; Ann Marie Schmidt Journal: J Clin Transl Endocrinol Date: 2017-08-14