Affiliations: Laboratoire de biologie vasculaire et cellulaire, JE 1557, Paris 7, INSERM U76 and Institut National de la Transfusion Sanguine, Paris, France
Note: [] Corresponding author: J.L. Wautier, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75739 Paris cedex 15, France. Tel.: +33 1 44 49 30 36; Fax: +33 1 43 06 04 83; E‐mail: wautier@ints.fr.
Abstract: The diabetic vasculopathy is one of the major complications responsible for the high incidence of arteriopathy, coronary ischemia and renal failure. Several hypothesis have been formulated to explain the vascular abnormalities. We recently showed that advanced glycation end products (AGE) have a pivotal role in the genesis of vascular dysfunction. AGE bind to a receptor (RAGE) present on endothelial cells. AGE binding to RAGE produced an oxidant stress and diminished vascular barrier function, increased vascular permeability, enhanced the expression of vascular cell adhesion molecule 1 (VCAM‐1). VCAM‐1 expression on endothelial cell and increased expression of CD11b CD18 on monocytes may facilitate monocyte emigration and can represent one of the initial steps of vascular alteration. In diabetic animals or in ApoE null diabetic mice which developed atherosclerosis, the infusion of recombinant RAGE prepared in insect cells was studied. Recombinant RAGE administration corrected vascular hyperpermeability and prevented the development of atherosclerosis in the animals.
