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Calcium regulation plays a key role in vascular function and has been implicated in aging-related hypercontractility of corpus cavernosum. We aimed to evaluate stromal interaction molecule (STIM)\/Orai system involvement in aging-related vascular alterations in the human macro and microvasculature. Aortae specimens and mesenteric arteries (MA), obtained from 45 organ donors, were functionally evaluated in organ chambers and wire myographs. Subjects were divided into groups either younger or older than 65-years old. The expressions of STIM-1, Orai1, and Orai3 were determined by immunofluorescence in the aorta and MA, and by Western blot in the aorta homogenates. The inhibition of STIM\/Orai with YM-58483 (20 \u03bcM) reversed adrenergic hypercontractility in MA from older subjects but did not modify aging-related hypercontractility in the aortic strips. Aging was related to an increased expression of Orai1 in human aorta, while Orai1 and STIM-1 were upregulated in MA. STIM-1 and Orai1 protein expressions were inversely correlated to endothelial function in MA. Circulating levels of Orai1 were correlated with the inflammatory factor TNF-\u03b1 and with the endothelial dysfunction marker asymmetric dimethylarginine. Aging is associated with an increased expression of the STIM\/Orai system in human vessels with functional relevance only in the microvascular territory, suggesting its role in aging-related microvascular dysfunction.<\/jats:p>","DOI":"10.3390\/cells11223675","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T03:11:21Z","timestamp":1669000281000},"page":"3675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Functional Role of STIM-1 and Orai1 in Human Microvascular Aging"],"prefix":"10.3390","volume":"11","author":[{"given":"Mariam","family":"El Assar","sequence":"first","affiliation":[{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica, Hospital Universitario de Getafe, 28905 Getafe, 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":"Esther","family":"Garc\u00eda-Rojo","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Hospital Universitario 12 de Octubre, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Sevilleja-Ortiz","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica, 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"}]},{"given":"Argentina","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Servicio de Histolog\u00eda-Investigaci\u00f3n, Unidad de Investigaci\u00f3n Traslacional en Cardiolog\u00eda (IRYCIS-UFV), Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borja","family":"Garc\u00eda-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Hospital Universitario 12 de Octubre, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Romero-Otero","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Hospital Universitario 12 de Octubre, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3789-9465","authenticated-orcid":false,"given":"Javier","family":"Angulo","sequence":"additional","affiliation":[{"name":"Servicio de Histolog\u00eda-Investigaci\u00f3n, Unidad de Investigaci\u00f3n Traslacional en Cardiolog\u00eda (IRYCIS-UFV), Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"H890","DOI":"10.1152\/ajpheart.00416.2017","article-title":"Endothelial Cell Senescence with Aging in Healthy Humans: Prevention by Habitual Exercise and Relation to Vascular Endothelial Function","volume":"313","author":"Rossman","year":"2017","journal-title":"Am. 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