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Overexpression of LOXIN Protects Endothelial Progenitor Cells From Apoptosis Induced by Oxidized Low Density Lipoprotein

Lookup NU author(s): Dr Naomi Willis


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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 g/mL. All hEPC apoptosed at 200 g/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.

Publication metadata

Author(s): Veas C, Jara C, Willis ND, Perez-Contreras K, Gutierrez N, Toledo J, Fernandez P, Radojkovic C, Zuniga FA, Escudero C, Aguayo C

Publication type: Article

Publication status: Published

Journal: Journal of Cardiovascular Pharmacology

Year: 2016

Volume: 67

Issue: 4

Pages: 326-335

Print publication date: 01/04/2016

Acceptance date: 01/01/1900

ISSN (print): 0160-2446

ISSN (electronic): 1533-4023

Publisher: Lippincott Williams & Wilkins, Ltd.


DOI: 10.1097/FJC.0000000000000358


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Funder referenceFunder name
1245-EM.TES (12.21)INNOVA BIOBIO, Chile
12IDL2-13351INNOVA CORFO Chile
DIUC 211.072.034-1.0Direccion de Investigacion, Universidad de Concepcion, Chile
UCO1201Convenio de desempeno, Universidad de Concepcion