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dc.contributor.author | Elbatreek, Mahmoud |
dc.contributor.author | Sadegh, Sepideh |
dc.contributor.author | Anastasi, Elisa |
dc.contributor.author | Guney, Emre |
dc.contributor.author | Nogales, Cristian |
dc.contributor.author | Kacprowski, Tim |
dc.contributor.author | Hassan, Ahmed |
dc.contributor.author | Teubner, Andreas |
dc.contributor.author | Huang, Po-Hsun |
dc.contributor.author | Hsu, Chien-Yi |
dc.contributor.author | Schiffers, Paul M. H. |
dc.contributor.author | Janssen, Ger M. |
dc.contributor.author | Kleikers, Pamela W. M. |
dc.contributor.author | Wipat, Anil |
dc.contributor.author | Baumbach, Jan |
dc.contributor.author | De Mey, Jo G.R. |
dc.contributor.author | Schmidt, Harald H.H.W. |
dc.date.accessioned | 2022-01-28T08:01:09Z |
dc.date.available | 2022-01-28T08:01:09Z |
dc.date.issued | 2020 |
dc.identifier.citation | Elbatreek MH, Sadegh S, Anastasi E, Guney E, Nogales C, Kacprowski T, et al. NOX5-induced uncoupling of endothelial NO synthase is a causal mechanism and theragnostic target of an age-related hypertension endotype. PLoS Biol. 2020 Nov 10; 18(11): e3000885. DOI: 10.1371/journal.pbio.3000885 |
dc.identifier.issn | 1544-9173 |
dc.identifier.uri | http://hdl.handle.net/10230/52349 |
dc.description.abstract | Hypertension is the most important cause of death and disability in the elderly. In 9 out of 10 cases, the molecular cause, however, is unknown. One mechanistic hypothesis involves impaired endothelium-dependent vasodilation through reactive oxygen species (ROS) formation. Indeed, ROS forming NADPH oxidase (Nox) genes associate with hypertension, yet target validation has been negative. We re-investigate this association by molecular network analysis and identify NOX5, not present in rodents, as a sole neighbor to human vasodilatory endothelial nitric oxide (NO) signaling. In hypertensive patients, endothelial microparticles indeed contained higher levels of NOX5-but not NOX1, NOX2, or NOX4-with a bimodal distribution correlating with disease severity. Mechanistically, mice expressing human Nox5 in endothelial cells developed-upon aging-severe systolic hypertension and impaired endothelium-dependent vasodilation due to uncoupled NO synthase (NOS). We conclude that NOX5-induced uncoupling of endothelial NOS is a causal mechanism and theragnostic target of an age-related hypertension endotype. Nox5 knock-in (KI) mice represent the first mechanism-based animal model of hypertension. |
dc.format.mimetype | application/pdf |
dc.language.iso | eng |
dc.publisher | Public Library of Science (PLoS) |
dc.rights | Copyright © 2020 Elbatreek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.subject.other | Hipertensió |
dc.subject.other | Persones grans -- Mortalitat |
dc.subject.other | Genètica |
dc.title | NOX5-induced uncoupling of endothelial NO synthase is a causal mechanism and theragnostic target of an age-related hypertension endotype |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | http://dx.doi.org/10.1371/journal.pbio.3000885 |
dc.rights.accessRights | info:eu-repo/semantics/openAccess |
dc.type.version | info:eu-repo/semantics/publishedVersion |