{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T17:17:36Z","timestamp":1778606256017,"version":"3.51.4"},"reference-count":80,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01339"],"award-info":[{"award-number":["PI19\/01339"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00502"],"award-info":[{"award-number":["PI19\/00502"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/02082"],"award-info":[{"award-number":["PI16\/02082"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/01619"],"award-info":[{"award-number":["PI16\/01619"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Aging impairs vascular function, but the mechanisms involved are unknown. The aim of this study was to analyze whether aging-related hyperphosphatemia is implied in this effect by elucidating the role of oxidative stress. C57BL6 mice that were aged 5 months (young) and 24 months (old), receiving a standard (0.6%) or low-phosphate (0.2%) diet, were used. Isolated mesenteric arteries from old mice showed diminished endothelium-dependent vascular relaxation by the down-regulation of NOS3 expression, increased inflammation and increased fibrosis in isolated aortas, compared to those isolated from young mice. In parallel, increased Nox4 expression and reduced Nrf2, Sod2-Mn and Gpx1 were found in the aortas from old mice, resulting in oxidant\/antioxidant imbalance. The low-phosphate diet improved vascular function and oxidant\/antioxidant balance in old mice. Mechanisms were analyzed in endothelial (EC) and vascular smooth muscle cells (SMCs) treated with the phosphate donor \u00df-glycerophosphate (BGP). In EC, BGP increased Nox4 expression and ROS production, which reduced NOS3 expression via NF\u03baB. BGP also increased inflammation in EC. In SMC, BGP increased Collagen I and fibronectin expression by priming ROS production and NF\u03baB activity. In conclusion, hyperphosphatemia reduced endothelium-dependent vascular relaxation and increased inflammation and vascular fibrosis through an impairment of oxidant\/antioxidant balance in old mice. A low-phosphate diet achieved improvements in the vascular function in old mice.<\/jats:p>","DOI":"10.3390\/antiox10081308","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T09:58:06Z","timestamp":1629367086000},"page":"1308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Hyperphosphatemia-Induced Oxidant\/Antioxidant Imbalance Impairs Vascular Relaxation and Induces Inflammation and Fibrosis in Old Mice"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0561-8275","authenticated-orcid":false,"given":"Ana","family":"Asenjo-Bueno","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n de la Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Universitario Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares, 28805 Madrid, Spain"},{"name":"Departamento Biolog\u00eda de Sistemas, Universidad de Alcal\u00e1, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Alcalde-Est\u00e9vez","sequence":"additional","affiliation":[{"name":"Departamento Biolog\u00eda de Sistemas, Universidad de Alcal\u00e1, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariam","family":"El Assar","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Universitario de Getafe, Getafe, 28905 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Olmos","sequence":"additional","affiliation":[{"name":"Departamento Biolog\u00eda de Sistemas, Universidad de Alcal\u00e1, Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n Nefrol\u00f3gica (IRSIN) de la Fundaci\u00f3n Renal I\u00f1igo \u00c1lvarez de Toledo (FRIAT), 28003 Madrid, Spain"},{"name":"Area 3-Fisiolog\u00eda y Fisiopatolog\u00eda Renal y Vascular del IRYCIS, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Plaza","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n de la Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Universitario Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares, 28805 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Sosa","sequence":"additional","affiliation":[{"name":"Departamento Biolog\u00eda de Sistemas, Universidad de Alcal\u00e1, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Mart\u00ednez-Miguel","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n de la Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Universitario Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares, 28805 Madrid, Spain"},{"name":"Servicio de Nefrolog\u00eda del Hospital Universitario Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares, 28805 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Piedad","family":"Ruiz-Torres","sequence":"additional","affiliation":[{"name":"Departamento Biolog\u00eda de Sistemas, Universidad de Alcal\u00e1, Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n Nefrol\u00f3gica (IRSIN) de la Fundaci\u00f3n Renal I\u00f1igo \u00c1lvarez de Toledo (FRIAT), 28003 Madrid, Spain"},{"name":"Area 3-Fisiolog\u00eda y Fisiopatolog\u00eda Renal y Vascular del IRYCIS, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0045-1680","authenticated-orcid":false,"given":"Susana","family":"L\u00f3pez-Ongil","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n de la Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Universitario Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares, 28805 Madrid, Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n Nefrol\u00f3gica (IRSIN) de la Fundaci\u00f3n Renal I\u00f1igo \u00c1lvarez de Toledo (FRIAT), 28003 Madrid, Spain"},{"name":"Area 3-Fisiolog\u00eda y Fisiopatolog\u00eda Renal y Vascular del IRYCIS, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1042\/CS20100476","article-title":"Aging and vascular endothelial function in humans","volume":"120","author":"Seals","year":"2011","journal-title":"Clin. 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