The different isoforms of the receptor for advanced glycation end products are modulated by pharmacological agents
Issue title: Selected Proceedings of the 15th Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM), June 28–July 1, 2009, Pontresina, Switzerland
Affiliations: Cellular and Vascular Biology, Paris7/Denis Diderot University, INTS, Paris, France | Department of Vascular Aging Biology, University Hospital of Lille, Lille, France | Inserm U665, Paris, France | Lariboisière Hospital, Paris, France
Note: [] Corresponding author: 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: jlwautier@ints.fr
Abstract: Elevated glucose concentration increases oxidation and Advanced Glycation End product (AGE) formation. The binding of circulatory AGEs or AGEs included in erythrocyte membrane to the receptor for AGEs (RAGE) generates in endothelial cells an oxidative stress and enhances the expression of inflammatory molecules. Engagement of RAGE by AGEs and subsequent signaling plays an important role in the development of diabetic complications. Soluble RAGE isoforms (sRAGE) neutralize the ligand-mediated damage by acting as a decoy. If the expression of RAGE is upregulated during the pathogenesis of inflammatory diseases, sRAGE mostly found decreased when complications ensue. By modulating RAGE isoform expression, it could be possible to reduce the incidence of complications. This review focused on the capability of Angiotensin Receptor Blockers (ARBs), which are used to treat patients with hypertension and/or diabetes, to modulate RAGE isoform expression because some data reported the interference with RAGE downstream. In this regard, three ARBs – irbesartan, telmisartan, candesartan cilexetil – were tested and provided evidence for their ability to inhibit in human endothelial cells the expression of membrane-bound and soluble RAGE isoforms induced by the inflammatory factor Tumor Necrosis Factor-α (TNF-α), demonstrating the potential benefits of these molecules in RAGE-oriented therapies. Modulating RAGE isoforms expression by correcting endothelial dysfunction is achievable by drugs already used for hypertension or diabetes treatment such as ARBs.
Keywords: Receptor for advanced glycation end products (RAGE), soluble RAGE (sRAGE), oxidative stress, angiotensin receptor blocker (ARB)
