Cortés-Jiménez, A. (Adriana)
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- NADPH oxidase 5 (NOX5) overexpression promotes endothelial dysfunction via cell apoptosis, migration, and metabolic alterations in human brain microvascular endothelial cells (hCMEC/D3)(2022) Martínez-Azcona, M. (María); Ainzúa-Pérez, E. (Elena); Orbe, J. (Josune); Fernandez-Irigoyen, J. (Joaquín); Marqués-Cantero, J. (Javier); Cortés-Jiménez, A. (Adriana); Roncal, C. (Carmen); Zalba, G. (Guillermo); Santamaria, E. (Enrique)NADPH oxidases (NOX) constitute the main reactive oxygen species (ROS) source in blood vessels. An oxidative stress situation due to ROS overproduction can lead into endothelial dysfunction, a molecular mechanism that precedes cardiovascular diseases (CVDs) such as atherosclerosis, myocardial infarction, and stroke. NOX5 is the last discovered member of the NOX family, studied in a lesser extent due to its absence in the rodent genome. Our objective was to describe the phenotypic alterations produced by an oxidative stress situation derived from NOX5 overexpression in an endothelial in vitro model. The in vitro model consists of the hCMEC/D3 cell line, derived from brain microvascular endothelium, infected with a recombinant NOX5-beta adenovirus. After an initial proteomic analysis, three phenotypic alterations detected in silico were studied: cell proliferation and apoptosis, general and mitochondrial metabolism, and migration capacity. NOX5 infection of hCMEC/D3 generates a functional protein and an increase in ROS production. This model produced changes in the whole cell proteome. The in silico analysis together with in vitro validations demonstrated that NOX5 overexpression inhibits proliferation and promotes apoptosis, metabolic alterations and cell migration in hCMEC/D3 cells. NOX5 overexpression in endothelial cells leads to phenotypic changes that can lead to endothelial dysfunction, the onset of atherosclerosis, myocardial infarction, and stroke.
- Expression of endothelial NOX5 alters the integrity of the blood-brain barrier and causes loss of memory in aging mice(2021) Abellanas-Sánchez, M.A. (Miguel Ángel); Ramirez, M.J. (María Javier); Aymerich-Soler, M.S. (María Soledad); Solas, M. (Maite); Pejenaute-Martínez-de-Lizarrondo, Á. (Álvaro); García-Lacarte, M. (Marcos); Marqués-Cantero, J. (Javier); Cortés-Jiménez, A. (Adriana); Zalba, G. (Guillermo)Blood-Brain barrier (BBB) disruption is a hallmark of central nervous system (CNS) dysfunction, and oxidative stress is one of the molecular mechanisms that may underlie this process. NADPH oxidases (NOX) are involved in oxidative stress-mediated vascular dysfunction and participate in the pathophysiology of its target organs. The NADPH oxidase 5 (NOX5) isoform is absent in rodents, and although little is known about the role it may play in disrupting the BBB, it has recently been implicated in experimental stroke. Our aim was to investigate the role of NADPH oxidase 5 (NOX5) in promoting vascular alterations and to identify its impact on the cognitive status of aged mice. No differences were detected in the arterial blood pressure or body weight between knock-in mice expressing endothelial NOX5 and the control mice. The Morris water maze test showed memory impairments in the aged knock-in mice expressing NOX5 compared with their control littermates. For assessing the BBB integrity, we studied the protein expression of two tight junction (TJ) proteins: Zonula occludens-1 (ZO-1) and occludin. Compared to the control animals, Aged NOX5 mice exhibited reduced levels of both proteins, demonstrating an alteration of the BBB integrity. Our data indicate that vascular NOX5 may favor behavioral changes with aging through oxidative stress-mediated BBB breakdown.