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Although many SERCA2a-related genes and proteins involved in the regulation of myocardial Ca<jats:sup>2+<\/jats:sup>fluxes have been explored, its related metabolites remain poorly studied. Our main objective was to identify circulating SERCA2a-related metabolites altered in cardiac allograft rejection and to determine whether these could serve as non-invasive biomarkers. Sixty plasma samples from adult heart transplant were included in a metabolomic analysis. Sphingosine-1 phosphate (S1P), metabolite closely related with SERCA, were increased in patients with cardiac rejection (p\u2009&lt;\u20090.0001). S1P discriminated between patients with and without rejection: normal grafts vs. all rejecting grafts (AUC\u2009=\u20090.911, p\u2009&lt;\u20090.0001), normal grafts vs. Grade 1\u2009R (AUC\u2009=\u20090.819, p\u2009&lt;\u20090.01), Grade 2\u2009R (AUC\u2009=\u20090.911, p\u2009&lt;\u20090.0001), Grade 3\u2009R (AUC\u2009=\u20090.996, p\u2009&lt;\u20090.0001). In addition, we found changes in key enzymes and receptors of S1P pathway analysed on explanted hearts from heart failure patients. This preliminary study reveals that circulating S1P determination could be a novel approach to detect cardiac rejection, showing a robust capability for detection that improves gradually with the severity of rejection. These alterations could be relevant to better understand the involvement of calcium regulation on the pathophysiology of rejection.<\/jats:p>","DOI":"10.1038\/s41598-019-50413-8","type":"journal-article","created":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T10:03:33Z","timestamp":1569405813000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection"],"prefix":"10.1038","volume":"9","author":[{"given":"Estefan\u00eda","family":"Taraz\u00f3n","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Gil-Cayuela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Garc\u00eda","family":"Manzanares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Roca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"Lago","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Ram\u00f3n","family":"Gonz\u00e1lez-Juanatey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"S\u00e1nchez-Lacuesta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Mart\u00ednez-Dolz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4415-7160","authenticated-orcid":false,"given":"Manuel","family":"Portol\u00e9s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Rosell\u00f3-Llet\u00ed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,9,25]]},"reference":[{"key":"50413_CR1","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/j.healun.2012.08.002","volume":"31","author":"J Stehlik","year":"2012","unstructured":"Stehlik, J. et al. 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