title: Endogenous secretory RAGE in obese women: association with platelet activation and oxidative stress.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors: Internal Medicine and Center of Excellence on Aging, Gabriele d'Annunzio University of Chieti, 66013 Chieti, Italy.
authors: Natale
authors: N
authors: Vazzana
authors: Maria Teresa
authors: MT
authors: Guagnano
authors: Chiara
authors: C
authors: Cuccurullo
authors: Elisabetta
authors: E
authors: Ferrante
authors: Stefano
authors: S
authors: Lattanzio
authors: Rossella
authors: R
authors: Liani
authors: Mario
authors: M
authors: Romano
authors: Giovanni
authors: G
authors: Davì
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000886:Anthropometry; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006801:Humans; D016014:Linear Models; D015227:Lipid Peroxidation / Q000502:physiology; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D015539:Platelet Activation / Q000502:physiology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood / Q000378:metabolism*; D012306:Risk; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D015431:Weight Loss / Q000502:physiology
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D008055:Lipids; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D015237:Dinoprost