NADPH oxidase 5 (NOX5) overexpression promotes endothelial dysfunction via cell apoptosis, migration, and metabolic alterations in human brain microvascular endothelial cells (hCMEC/D3)

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 infarc...

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Authors: Marqués-Cantero, J. (Javier)|||/items/19f43fc2-15a8-4581-b206-48e41dac93f1, Fernandez-Irigoyen, J. (Joaquín)|||/items/700f4366-d68f-4161-af03-2cac47ea718d, Ainzúa-Pérez, E. (Elena)|||/items/a24267a0-145a-4cda-b4a4-0550e1ed03d3, Martínez-Azcona, M. (María)|||/items/315733ee-76ef-4ce3-8db6-a1b4515bf3af, Cortés-Jiménez, A. (Adriana)|||/items/c47d78ea-adf5-4f5b-8182-64d016a6168d, Roncal-Mancho, C. (Carmen)|||/items/6c0dc409-f0aa-412b-9d75-436ba8a0a4ff, Orbe-Lopategui, J. (Josune)|||/items/033ea7ef-1eff-418a-9fc4-1e2d3498d726, Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8, Zalba-Goñi, G. (Guillermo)|||/items/71410fa2-baa5-4efc-bce7-14b4b0e23802
Format: article
Publication Date:2022
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/65496
Online Access:https://hdl.handle.net/10171/65496
Access Level:Open access
Keyword:NADPH oxidase 5
Endothelial cells
Endothelial dysfunction
Cell proliferation
Cell migration
Mitochondrial dysfunction
Cardiovascular diseases
Description
Summary: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.

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