Anti-sRAGE autoimmunity in obesity: downturn after bariatric surgery is independent of previous diabetic status.

AIM: Morbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients. METHODS: After exclusion based on specific criteria, 150 subjects (50 normoglycemics, 50 glucose-intolerants and 50 diabetics) were randomly recruited from a cohort of 750 obese patients (ABOS). Serum sRAGE and anti-sRAGE autoantibodies were measured before bariatric surgery. Sixty-nine patients were followed for up to 1year after gastric bypass, and their levels of sRAGE and anti-sRAGE autoantibodies measured. The control group consisted of healthy blood donors. RESULTS: Compared with controls, baseline levels of sRAGE and anti-sRAGE autoantibodies were significantly higher in all obese patients independently of glucose regulation (P<0.001). At 1year after gastric bypass, sRAGE and anti-sRAGE were decreased (P<0.001). The decrease in anti-sRAGE autoantibodies was correlated with an increase in high-density lipoprotein (HDL; P=0.02). CONCLUSION: Independently of previous diabetic status, morbid obesity increases sRAGE and anti-sRAGE levels. Weight loss after gastric bypass is followed by a decrease in both titres. The decrease in anti-sRAGE correlates with an increase in HDL.

Advanced glycation end-products: implications for diabetic and non-diabetic nephropathies.

Glycation is the process whereby sugars bind to the free amine residues of proteins. These newly formed modified molecular species are known as 'advanced glycation end-products', or AGEs. AGE toxicity may occur through at least three mechanisms: interaction with the receptor for AGEs (RAGE); tissue deposition; and in situ glycation. AGEs trigger proinflammatory, profibrotic and procoagulant cellular responses that are capable of damaging tissues, often targeting particular organs. In diabetic patients, the conditions needed to promote AGE formation are all present, and are further accentuated by accompanying renal failure. The aim of this review is to outline the involvement of AGEs in the various forms of renal pathology associated with diabetic and non-diabetic nephropathies. AGEs are present in all renal compartments in diabetic patients, including the vessels, glomeruli, tubules and interstitium. Many cell types may be activated-specifically, endothelial, tubular and mesangial cells, and podocytes. AGEs play a major role in the accumulation of extracellular matrix, as occurs in diabetic glomerulosclerosis, and are also involved in most diabetic (renovascular, microangiopathic and glomerular) and non-diabetic renal injury associated with progressive glomerulosclerosis and ageing.

Peritoneal, aging during PD: implication of RAGE,the receptor for AGEs / No disponible

During last years, the number of patients who have been continuously treated by peritoneal dialysis (PD) for over 5 or 10 years has markedly increased. Sclerosing syndromes and membrane failure are the most common complications that are now currently observed in long-term PD patients. Exposure to conventional PD fluids (PDFs) with poor biocompatibility induces a kind of «chemical peritonitis» in response of bad «biotolerance». The peritoneal fibroblasts, mesothelial cells and especially endothelial cells function as a filtration barrier, but also control intraperitoneal inflammation as well as leukocytes and macrophages. Peritoneal exposure to conventional poorly biocompatible PDFs which combine non-physiological pH, high glucose concentrations, and high levels of glucose degradation products (GDPs), is associated with an accelerated peritoneal aging. Heat sterilization of PDFs induces the formation of GDPs which are involved in the formation of advanced glycation end-products (AGEs).Glucose, GDPs and AGEs participate to the peritoneal membrane failure and aging. AGEs via RAGE (receptor for AGEs) are involved in human peritoneal mesothelial cell (HPMC) activation. In the present work, we summarize our previous in vitro works regarding mesothelial RAGE implication in the peritoneal membrane aging. Two periods of aging are distinguished: i) early peritoneal changes related to mesothelial cell activation and loss, ii)late membrane alteration correlated to submesothelial fibrosis and neovascularization (AU)

En los últimos años ha aumentado considerablemente el número de pacientes tratados de manera continua con diálisis peritoneal (DP) durante 5 ó 10 años. Los síndromes esclerosantes y el fracaso de la membrana son las complicaciones más frecuentes que se observan actualmente en los pacientes que reciben DP a largo plazo. La exposición a líquidos de(LDP) convencionales con escasa biocompatibilidad induce un tipo de «peritonitis química» en respuesta a una mala «biotolerancia». Los fibroblastos peritoneales, las células mesoteliales y, en especial, las células endoteliales funcionan como una barrera de filtración, pero también controlan la inflamación intraperitoneal y los leucocitos y macrófagos. La exposición peritoneal a LDP convencionales poco biocompatibles, que combinan pH no fisiológico, elevadas concentraciones de glucosa y grandes cantidades de productos de degradación de la glucosa (PDG), acelera el envejecimiento peritoneal. La esterilización por calor de los LDP induce la formación de PDG que están implicados en la formación de productos terminales de glucosilación avanzada (PTGA). La glucosa, los PDG y los PTGA participan en el fracaso y el envejecimiento de la membrana peritoneal. Los PTGA a través de RPTGA (receptor de PTGA) intervienen en la activación de las células mesoteliales peritoneales humanas (CMPH).En el presente trabajo resumimos nuestros estudios anteriores in vitro sobre la implicación del RPTGA mesotelial en el envejecimiento de la membrana peritoneal. Se distinguiendo periodos de envejecimiento: i) alteraciones peritoneales precoces relacionadas con la activación y pérdida de células mesoteliales, ii) alteración tardía de la membrana relacionada con fibrosis y neovascularización submesoteliales (AU)

Peritoneal aging during PD: implication of RAGE, the receptor for AGEs.

During last years, the number of patients who have been continuously treated by peritoneal dialysis (PD) for over 5 or 10 years has markedly increased. Sclerosing syndromes and membrane failure are the most common complications that are now currently observed in long-term PD patients. Exposure to conventional PD fluids (PDFs) with poor biocompatibility induces a kind of <> in response of bad <>. Theperitoneal fibroblasts, mesothelial cells and especially endothelial cells function as a filtration barrier, but also control intraperitoneal inflammation as well as leukocytes and macrophages.Peritoneal exposure to conventional poorly biocompatible PDFs which combine non-physiological pH, high glucose concentrations,and high levels of glucose degradation products (GDPs), is associated with an accelerated peritoneal aging. Heat sterilization of PDFs induces the formation of GDPs which are involved in the formation of advanced glycation end-products (AGEs).Glucose, GDPs and AGEs participate to the peritoneal membrane failure and aging. AGEs via RAGE (receptor for AGEs) are involved in human peritoneal mesothelial cell (HPMC) activation.In the present work, we summarize our previous in vitro works regarding mesothelial RAGE implication in the peritoneal membrane aging. Two periods of aging are distinguished: i) early peritoneal changes related to mesothelial cell activation and loss, ii)late membrane alteration correlated to submesothelial fibrosis and neovascularization.