{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:44:28Z","timestamp":1792201468628,"version":"4.4.0"},"reference-count":55,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Junta de Extremadura research","award":["IB18020"],"award-info":[{"award-number":["IB18020"]}]},{"name":"Junta de Extremadura research","award":["GR24034"],"award-info":[{"award-number":["GR24034"]}]},{"DOI":"10.13039\/501100004837","name":"MCIN","doi-asserted-by":"crossref","award":["PID2022-136279NB-C21"],"award-info":[{"award-number":["PID2022-136279NB-C21"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>STC2 (stanniocalcin 2) controls calcium (Ca2+) homeostasis in human platelets and other cell lines. The regulation of intracellular Ca2+ homeostasis is crucial for platelet activation; thus, the alteration in intracellular Ca2+ concentration or the mechanism involved in its regulation has been proposed to underlie some thrombotic disorders. Our previous studies evidenced that the knockdown of STC2 altered murine platelet activation; furthermore, a reduction in STC2 expression resulted in enhanced Ca2+ homeostasis in diabetic patients and, therefore, would contribute to the prothrombotic condition as a hallmark of diabetes mellitus type 2 (DM2). In this study, we examine a possible link between the expression of stanniocalcins (STCs) and different thrombotic events in humans. The expression of STCs was determined by Western blotting (WB); meanwhile, the analysis of protein interaction and phosphorylation was performed by completing a previous immunoprecipitation protocol (IP) of the proteins of interest. Thus, our results from patients with stroke\/ictus presented a clear reduction in STC2 expression in their platelets, finding less STC2 content in the youngest thrombotic patients. Furthermore, acetyl-salicylic acid (ASA) administration reversed the decrease in the expression of STC2 in patients who did not suffer additional thrombotic episodes, as evidenced by the longitudinal analysis of up to 10 years of follow-up. Additionally, the increase in STC2 phosphorylation at the serine residues revealed increased activity of STC2 in thrombotic patients. Finally, we suggest that store-operated Ca2+ entry (SOCE) is over-activated in patients suffering from stroke\/ictus, as revealed by the increase in the STIM1\/Orai1 interaction found under resting conditions and, further, because MEG-01 cells transfected with siRNA STC2 to evoke artificial reduction in the STC2 expression presented an increased SOCE with respect to the control cells transfected with siRNA A. Conversely, the expression of the non-capacitative Ca2+ channels, Orai3 and TRPC6, was found to be reduced in patients with stroke. Altogether, our data allow us to conclude that STC2 represents a promising marker of stroke\/ictus in thrombotic patients.<\/jats:p>","DOI":"10.3390\/ijms26209999","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T15:20:12Z","timestamp":1760973612000},"page":"9999","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Stanniocalcin2, A Promising New Target for Identifying Patients with Stroke\/Ictus"],"prefix":"10.3390","volume":"26","author":[{"given":"Nuria","family":"Bermejo","sequence":"first","affiliation":[{"name":"Department of Hematology, Hospital San Pedro de Alc\u00e1ntara, 10005 C\u00e1ceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5234-1478","authenticated-orcid":false,"given":"Jos\u00e9 Javier","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Extremadura, 10003 C\u00e1ceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Berna-Erro","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Miguel Hern\u00e1ndez, 03202 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esperanza","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Blood Donation Center, Extremadura County Health Service, 06800 M\u00e9rida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Jes\u00fas","family":"Corbacho","sequence":"additional","affiliation":[{"name":"Blood Donation Center, Extremadura County Health Service, 06800 M\u00e9rida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Blood Donation Center, Extremadura County Health Service, 06800 M\u00e9rida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Purificaci\u00f3n","family":"Granados","sequence":"additional","affiliation":[{"name":"Pharmacy Unit, Extremadura County Health Service, 10004 C\u00e1ceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2067-2627","authenticated-orcid":false,"given":"Pedro Cosme","family":"Redondo","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Extremadura, 10003 C\u00e1ceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, June 20). 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