{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:10:36Z","timestamp":1790478636429,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T00:00:00Z","timestamp":1693267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Economy and Competitiveness","award":["PI15\/01160"],"award-info":[{"award-number":["PI15\/01160"]}]},{"name":"Ministry of Economy and Competitiveness","award":["PI15\/00674"],"award-info":[{"award-number":["PI15\/00674"]}]},{"name":"Ministry of Economy and Competitiveness","award":["PI20\/00977"],"award-info":[{"award-number":["PI20\/00977"]}]},{"name":"Ministry of Economy and Competitiveness","award":["CB16\/10\/00464"],"award-info":[{"award-number":["CB16\/10\/00464"]}]},{"name":"FEDER","award":["PI15\/01160"],"award-info":[{"award-number":["PI15\/01160"]}]},{"name":"FEDER","award":["PI15\/00674"],"award-info":[{"award-number":["PI15\/00674"]}]},{"name":"FEDER","award":["PI20\/00977"],"award-info":[{"award-number":["PI20\/00977"]}]},{"name":"FEDER","award":["CB16\/10\/00464"],"award-info":[{"award-number":["CB16\/10\/00464"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vascular territories display heterogeneous sensitivity to the impacts of aging. The relevance of the STIM\/Orai system to vascular function depends on the vascular bed. We aimed to evaluate the contribution of the STIM\/Orai system to aging-related vascular dysfunction in rat coronary circulation. Vascular function was evaluated according to myography in coronary arteries from young (three-month-old) and older (twenty-month-old) rats. The effects of aging and STIM\/Orai inhibition on the contraction and relaxation of the coronary arteries and on the protein expression of STIM-1, Orai1, and Orai3 in these vessels were determined. Aging-related hypercontractility to serotonin and endothelin-1 in arteries from male rats was reversed by STIM\/Orai inhibition with YM-58483 or by specifically blocking the Orai1 channel with Synta66. The inhibitory effects of Synta66 on coronary vasoconstriction were also observed in older female rats. YM-58483 relaxed serotonin- but not KCl-contracted arteries from males. STIM\/Orai inhibition improved defective endothelial vasodilations in aged arteries, even in the presence of NO synthase and cyclooxygenase inhibitors, but not in KCl-contracted segments. YM-58483 significantly enhanced relaxations to calcium-activated potassium channel stimulation in aged vessels. Increased protein expression of Orai1 and Orai3 was detected in arterial homogenates and sections from older rats. Upregulation of the Orai channel contributes to aging-related coronary dysfunction, revealing a potential target in reducing CVD risk.<\/jats:p>","DOI":"10.3390\/ijms241713402","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T08:26:52Z","timestamp":1693297612000},"page":"13402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Upregulation of Orai Channels Contributes to Aging-Related Vascular Alterations in Rat Coronary Arteries"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3789-9465","authenticated-orcid":false,"given":"Javier","family":"Angulo","sequence":"first","affiliation":[{"name":"Servicio de Histolog\u00eda, Unidad de Investigaci\u00f3n Cardiovascular (IRYCIS\/UFV), Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argentina","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Servicio de Histolog\u00eda, Unidad de Investigaci\u00f3n Cardiovascular (IRYCIS\/UFV), Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Sevilleja-Ortiz","sequence":"additional","affiliation":[{"name":"Servicio de Histolog\u00eda, Unidad de Investigaci\u00f3n Cardiovascular (IRYCIS\/UFV), Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"S\u00e1nchez-Ferrer","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica, Hospital Universitario de Getafe, 28905 Getafe, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-1333","authenticated-orcid":false,"given":"Leocadio","family":"Rodr\u00edguez-Ma\u00f1as","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Servicio de Geriatr\u00eda, Hospital Universitario de Getafe, 28905 Getafe, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"El Assar","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica, Hospital Universitario de Getafe, 28905 Getafe, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.jacc.2019.11.061","article-title":"Mechanisms of Vascular Aging, A Geroscience Perspective: JACC Focus Seminar","volume":"75","author":"Ungvari","year":"2020","journal-title":"J. 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