title: Overexpression of LOXIN Protects Endothelial Progenitor Cells From Apoptosis Induced by Oxidized Low Density Lipoprotein.
abstract: Human endothelial progenitor cells (hEPC) are adult stem cells located in the bone marrow and peripheral blood. Studies have indicated that hEPC play an important role in the recovery and repair of injured endothelium, however, their quantity and functional capacity is reduced in several diseases including hypercholesterolemia. Recently, it has been demonstrated that hEPC express lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its activation by oxidized low-density lipoprotein (ox-LDL) induces cellular dysfunction and apoptosis. This study aimed to investigate whether overexpression of LOXIN, a truncated isoform of LOX-1 that acts as a dominant negative, plays a protective role against ox-LDL-induced apoptosis in hEPC. Human endothelial progenitor cells exposed to ox-LDL showed a significant increase in LOX-1 expression, and apoptosis began at ox-LDL concentrations above 50 μg/mL. All hEPC apoptosed at 200 μg/mL ox-LDL. High LOXIN expression was generated using adenoviral systems in hEPC and SiHa cells transduced with 100 colony-forming units per cell. Transduced LOXIN localized to the plasma membrane and blocked ox-LDL uptake mediated by LOX-1. Overexpression of LOXIN protected hEPC from ox-LDL-induced apoptosis, and therefore maybe a novel way of improving hEPC function and quantity. These results suggest that adenoviral vectors of LOXIN may provide a possible treatment for diseases related to ox-LDL and vascular endothelium dysfunction, including atherosclerosis.
authors.affiliation: *Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile; †Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; ‡Department of Physiopathology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile; §School of Medical Technology, Faculty of Health Sciences, San Sebastián University, Chile; ¶Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Department of Basic Sciences, University of Bio Bío, Chillán, Chile; and ‖Group of Research and Innovation in Vascular Health, University of Bio Bío, Chillán, Chile. (GRIVAS Health).
authors.forename: Carlos
authors.initials: C
authors.lastname: Veas
authors.forename: Casandra
authors.initials: C
authors.lastname: Jara
authors.forename: Naomi D
authors.initials: ND
authors.lastname: Willis
authors.forename: Karen
authors.initials: K
authors.lastname: Pérez-Contreras
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gutierrez
authors.forename: Jorge
authors.initials: J
authors.lastname: Toledo
authors.forename: Paulina
authors.initials: P
authors.lastname: Fernandez
authors.forename: Claudia
authors.initials: C
authors.lastname: Radojkovic
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Zuñiga
authors.forename: Carlos
authors.initials: C
authors.lastname: Escudero
authors.forename: Claudio
authors.initials: C
authors.lastname: Aguayo
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics*
chemical_list: D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein