{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:24:21Z","timestamp":1791361461218,"version":"4.3.1"},"reference-count":56,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Government of Navarra","award":["PC159-160-161 NOXICTUS"],"award-info":[{"award-number":["PC159-160-161 NOXICTUS"]}]},{"name":"Government of Navarra","award":["FPU19\/01807"],"award-info":[{"award-number":["FPU19\/01807"]}]},{"name":"Spanish Ministry of Universities","award":["PC159-160-161 NOXICTUS"],"award-info":[{"award-number":["PC159-160-161 NOXICTUS"]}]},{"name":"Spanish Ministry of Universities","award":["FPU19\/01807"],"award-info":[{"award-number":["FPU19\/01807"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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-\u03b2 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.<\/jats:p>","DOI":"10.3390\/antiox11112147","type":"journal-article","created":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T23:45:00Z","timestamp":1667087100000},"page":"2147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["NADPH Oxidase 5 (NOX5) Overexpression Promotes Endothelial Dysfunction via Cell Apoptosis, Migration, and Metabolic Alterations in Human Brain Microvascular Endothelial Cells (hCMEC\/D3)"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3075-8520","authenticated-orcid":false,"given":"Javier","family":"Marqu\u00e9s","sequence":"first","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Department of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-4099","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Fern\u00e1ndez-Irigoyen","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Clinical Neuroproteomics Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ainz\u00faa","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Department of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Mart\u00ednez-Azcona","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Department of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9474-8524","authenticated-orcid":false,"given":"Adriana","family":"Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Department of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0616-9600","authenticated-orcid":false,"given":"Carmen","family":"Roncal","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, Cima Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Cardiovascular\u2014CIBERCV, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-7670","authenticated-orcid":false,"given":"Josune","family":"Orbe","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, Cima Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"RICORS-Cerebrovascular Diseases, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8046-8102","authenticated-orcid":false,"given":"Enrique","family":"Santamar\u00eda","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Clinical Neuroproteomics Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-1523","authenticated-orcid":false,"given":"Guillermo","family":"Zalba","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Department of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1161\/ATVBAHA.117.309813","article-title":"Endothelial Functions","volume":"37","author":"Godo","year":"2017","journal-title":"Arter. 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