Affiliations: Department of Cellular and Vascular Biology, Paris 7/Denis Diderot University, Paris, France | Inserm U665, INTS, Paris, France | Lariboisière Hospital, Paris, France
Note: [] Address for correspondence: Prof. Jean-Luc Wautier, Laboratoire de Biologie Vasculaire et Cellulaire, Institut National de la Transfusion Sanguine (INTS), 6 Rue Alexandre Cabanel, 75015 Paris Cedex, France. Tel.: +33 1 44 49 30 01; Fax: +33 1 43 06 04 83; E-mail: [email protected].
Abstract: Red blood cell (RBC) adhesion to endothelium is increased in diabetes mellitus and is correlated with the severity of vascular complications. Microangiopathy is the most frequent complications in patients suffering from diabetes mellitus. Elevated glucose concentration increases the oxidation phenomenon and advanced glycation end product (AGE) formation. Plasma proteins, structural proteins and also RBC proteins can be glycated such as glycated hemoglobin and RBC membrane proteins. Interaction of plasmatic AGE or RBC bearing AGE with the receptor for AGE (RAGE) alters vascular function leading to a vascular hyperpermeability inflammatory reaction including oxidant stress and cytokine production. Reactive oxygen species (ROS) react with nitric oxide (NO) limiting its vasodilatory effect and NO synthase function is altered. All these factors may be at the origin of high blood pressure which is deleterious for the eye and kidney vasculature. AGE can act directly on vascular function but also through RAGE. AGE binding to RAGE alters endothelial cell function stimulating NADPH oxidase and reactive oxygen species production. Limiting oxidation, reducing AGE formation or interaction with RAGE is achievable by drugs already used for hypertension or diabetes, but new treatment by NO modulators may limit the deleterious effect of RBC adhesion to endothelium.
Keywords: Diabetic vasculopathy, nitric oxide, advanced glycation end products (AGE), reactive oxygen species, receptor for AGE (RAGE), red blood cells
DOI: 10.3233/BIR-2009-0519
Journal: Biorheology, vol. 46, no. 1, pp. 63-72, 2009
