Red blood cell adhesion in diabetes mellitus is mediated by advanced glycation end product receptor and is modulated by nitric oxide.
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.
Grossin
Nicolas
N
Department of Cellular and Vascular Biology, Paris 7/Denis Diderot University, Inserm U665, and Lariboisière Hospital, Paris, France.
Wautier
Marie-Paule
MP
Wautier
Jean-Luc
JL
D002448:Cell Adhesion; D003920:Diabetes Mellitus / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009569:Nitric Oxide