Oxidation of low density lipoproteins by myeloperoxidase at the surface of endothelial cells: an additional mechanism to subendothelium oxidation K. Zouaoui Boudjeltia a, * , N. Moguilevsky f , I. Legssyer d , S. Babar d , M. Guillaume a , P. Delree c , M. Vanhaeverbeek a , D. Brohee a , J. Ducobu e , C. Remacle b a Laboratoire de Me ´decine Expe ´rimentale (ULB 222 Unit) ISPPC Ho ˆpital Ve ´sale, Montigny-Le-Tilleul, Belgium b Laboratoire de Biologie Cellulaire, UCL, Louvain, Louvain-La-Neuve, Belgium c Institut de Pathologie et de Ge ´ne ´tique, Loverval, Belgium d Service de Ge ´ne ´tique Applique ´e, IBMM, Universite ´ Libre de Bruxelles, Gosselies, Belgium e Service de Me ´ decine Interne, CHU Tivoli, La Louvie `re, Belgium f Technology Transfer Office, University of Namur, Namur, Belgium Received 23 September 2004 Available online 28 October 2004 Abstract The present paradigm of atherogenesis proposes that low density lipoproteins (LDL) are trapped in subendothelial space of the vascular wall where they are oxidized. Myeloperoxidase (MPO) plays a key role in oxidative damage. We propose that LDL oxi- dation by myeloperoxidase (Mox-LDL) could occur at the surface of the endothelial cells and not restricted to the subendothelial space. The triad constituted by endothelial cells, circulating LDL and MPO in close interaction, constitutes a synergic mechanism for the genesis of Mox-LDL. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Myeloperoxidase; LDL; Endothelial cells; Mox-LDL Low density lipoproteins (LDL) and particularly their oxidized forms are thought to be a key element in atherosclerosis development. However, the precise physiological process for LDL oxidation in vivo is still unknown. The consensus theory of early atherosclerosis proposes that LDL are trapped in subendothelial space of the vascular wall where they can be oxidized by arte- rial wall cells [1]. Nevertheless, it has not been definitely ruled out that oxidation of LDL could also occur out- side the lesion sites. The working hypothesis used over several years is that myeloperoxidase (MPO) could be a key element for oxidative damage in the human artery wall. The presence of MPO and products of its activity has been observed in atherosclerotic lesions at various stages of severity [2,3]. Recent clinical studies in human support a role for MPO in atherogenesis. Two reports showed that patients presenting MPO-deficiency or a low level of blood MPO had a decreased cardiovascular risk [4,5]. Two other studies showed that the MPO serum levels predicted risks in patients with acute coronary syndromes or chest pain [6,7]. MPO is a protein secreted by activated phagocytes, which generates modified/oxi- dized (lipo)proteins via the production of hypochlorous acid (HOCl) from H 2 O 2 and chloride [8]. The oxidation of LDL by MPO leads mainly to modifications of apo- lipoproteins by formation of chlorotyrosine, dityrosine, and nitrotyrosine [9], the oxidation of the lipidic moiety 0006-291X/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.bbrc.2004.10.049 * Corresponding author. Fax: +32 71 924710. E-mail address: kaveroes@hotmail.com (K. Zouaoui Boudjeltia). www.elsevier.com/locate/ybbrc Biochemical and Biophysical Research Communications 325 (2004) 434–438 BBRC