title: Myeloperoxidase oxidized LDL interferes with endothelial cell motility through miR-22 and heme oxygenase 1 induction: possible involvement in reendothelialization of vascular injuries.
abstract: Cardiovascular disease linked to atherosclerosis is the leading cause of death worldwide. Atherosclerosis is mainly linked to dysfunction in vascular endothelial cells and subendothelial accumulation of oxidized forms of LDL. In the present study, we investigated the role of myeloperoxidase oxidized LDL (Mox-LDL) in endothelial cell dysfunction. We studied the effect of proinflammatory Mox-LDL treatment on endothelial cell motility, a parameter essential for normal vascular processes such as angiogenesis and blood vessel repair. This is particularly important in the context of an atheroma plaque, where vascular wall integrity is affected and interference with its repair could contribute to progression of the disease. We investigated in vitro the effect of Mox-LDL on endothelial cells angiogenic properties and we also studied the signalling pathways that could be affected by analysing Mox-LDL effect on the expression of angiogenesis-related genes. We report that Mox-LDL inhibits endothelial cell motility and tubulogenesis through an increase in miR-22 and heme oxygenase 1 expression. Our in vitro data indicate that Mox-LDL interferes with parameters associated with angiogenesis. They suggest that high LDL levels in patients would impair their endothelial cell capacity to cope with a damaged endothelium contributing negatively to the progression of the atheroma plaque.
authors.affiliation: Institute for Molecular Biology and Medicine (IBMM), Université Libre de Bruxelles, rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors.forename: Jalil
authors.initials: J
authors.lastname: Daher
authors.affiliation: Laboratory of Protein Signaling and Interactions, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, Avnue de l'Hopital 1 (B34), 4000 Sart-Tilman, Belgium.
authors.forename: Maud
authors.initials: M
authors.lastname: Martin
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), CHU de Charleroi, A. Vésale Hospital, Université Libre de Bruxelles, rue de Gozée 706, 6110 Montigny-le-Tilleul, Belgium.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Rousseau
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), CHU de Charleroi, A. Vésale Hospital, Université Libre de Bruxelles, rue de Gozée 706, 6110 Montigny-le-Tilleul, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Nuyens
authors.affiliation: Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 121, 1000 Bruxelles, Belgium.
authors.forename: Hussein
authors.initials: H
authors.lastname: Fayyad-Kazan
authors.affiliation: Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, Boulevard du Triomphe, Campus Plaine CP 205/5, 1050 Bruxelles, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Antwerpen
authors.affiliation: Creatis, CNRS UMR 5220, INSERM U1044, UCB Lyon1, INSA Lyon, University of Lyon, 7 Avenue Jean Capelle, 69621 Villeurbanne, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Courbebaisse
authors.affiliation: Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 121, 1000 Bruxelles, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Martiat
authors.affiliation: Laboratory of Immunology, Department of Biochemistry, Faculty of Sciences, Lebanese University, Hadath, Beirut 21219, Lebanon.
authors.forename: Bassam
authors.initials: B
authors.lastname: Badran
authors.affiliation: Laboratory of Protein Signaling and Interactions, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, Avnue de l'Hopital 1 (B34), 4000 Sart-Tilman, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Dequiedt
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), CHU de Charleroi, A. Vésale Hospital, Université Libre de Bruxelles, rue de Gozée 706, 6110 Montigny-le-Tilleul, Belgium.
authors.forename: Karim
authors.identifier: 0000-0002-7687-8579
authors.initials: K
authors.lastname: Zouaoui Boudjeltia
authors.affiliation: Institute for Molecular Biology and Medicine (IBMM), Université Libre de Bruxelles, rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium ; Laboratory of Experimental Medicine (ULB 222 Unit), CHU de Charleroi, A. Vésale Hospital, Université Libre de Bruxelles, rue de Gozée 706, 6110 Montigny-le-Tilleul, Belgium.
authors.forename: Luc
authors.identifier: 0000-0003-1087-8485
authors.initials: L
authors.lastname: Vanhamme
mesh_terms: D000818:Animals; D016466:CHO Cells; D002465:Cell Movement; D006224:Cricetinae; D003412:Cricetulus; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D009195:Peroxidase / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D015398:Signal Transduction; D057772:Vascular System Injuries / Q000378:metabolism; D014945:Wound Healing
chemical_list: D008077:Lipoproteins, LDL; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; C099252:oxidized low density lipoprotein; D009195:Peroxidase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1