{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T11:39:44Z","timestamp":1770982784501,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006692","name":"Universit\u00e0 degli Studi di Torino","doi-asserted-by":"publisher","award":["ex-60% Local funding"],"award-info":[{"award-number":["ex-60% Local funding"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM). Enhanced platelet reactivity is considered a main determinant of the increased atherothrombotic risk of diabetic patients. Thrombopoietin (THPO), a humoral growth factor able to stimulate megakaryocyte proliferation and differentiation, also modulates the response of mature platelets by enhancing both activation and binding to leukocytes in response to different agonists. Increased THPO levels have been reported in different clinical conditions characterized by a generalized pro-thrombotic state, from acute coronary syndromes to sepsis\/septic shock, and associated with elevated indices of platelet activation. To investigate the potential contribution of elevated THPO levels in platelet activation in T1DM patients, we studied 28 T1DM patients and 28 healthy subjects. We measured plasma levels of THPO, as well as platelet-leukocyte binding, P-selectin, and THPO receptor (THPOR) platelet expression. The priming activity of plasma from diabetic patients or healthy subjects on platelet\u2013leukocyte binding and the role of THPO on this effect was also studied in vitro. T1DM patients had higher circulating THPO levels and increased platelet\u2013monocyte and platelet\u2013granulocyte binding, as well as platelet P-selectin expression, compared to healthy subjects, whereas platelet expression of THPOR did not differ between the two groups. THPO concentrations correlated with platelet\u2013leukocyte binding, as well as with fasting glucose and Hb1Ac. In vitro, plasma from diabetic patients, but not from healthy subjects, primed platelet\u2013leukocyte binding and platelet P-selectin expression. Blocking THPO biological activity using a specific inhibitor prevented the priming effect induced by plasma from diabetic patients. In conclusion, augmented THPO may enhance platelet activation in patients with T1DM, potentially participating in increasing atherosclerotic risk.<\/jats:p>","DOI":"10.3390\/ijms22137032","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:52:46Z","timestamp":1624963966000},"page":"7032","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Thrombopoietin Contributes to Enhanced Platelet Activation in Patients with Type 1 Diabetes Mellitus"],"prefix":"10.3390","volume":"22","author":[{"given":"Ornella","family":"Bosco","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Vizio","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Gruden","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2738-9119","authenticated-orcid":false,"given":"Martina","family":"Schiavello","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bartolomeo","family":"Lorenzati","sequence":"additional","affiliation":[{"name":"Emergency Medicine, A.O. S. Croce e Carle, 12100 Cuneo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Cavallo-Perin","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2921-1763","authenticated-orcid":false,"given":"Isabella","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Montrucchio","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-1217","authenticated-orcid":false,"given":"Enrico","family":"Lupia","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shi, M., Tang, R., Huang, F., Zhong, T., Chen, Y., Li, X., and Zhou, Z. 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