{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:34:05Z","timestamp":1791045245642,"version":"4.1.0"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"10","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81873432"],"award-info":[{"award-number":["81873432"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82070143"],"award-info":[{"award-number":["82070143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Jiangsu Province of China","award":["ZDRCA2016047"],"award-info":[{"award-number":["ZDRCA2016047"]}]},{"name":"Natural Science Foundation of the Jiangsu Higher Education Institution of China","award":["18KJA320006"],"award-info":[{"award-number":["18KJA320006"]}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"crossref","award":["PAPD"],"award-info":[{"award-number":["PAPD"]}],"id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:p>Hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) involves in redox reactions. Considering the role of reactive oxygen species (ROS) in platelet function, whether it regulates platelet function remains unclear. Using an inhibitor of HIF prolyl\u2013hydroxylase, IOX-2, we intend to investigate its effect on platelet function. Human platelets were treated with IOX-2 (0, 10, 25, and 50 \u03bcM) followed by analysis of platelet aggregation, granule secretion, receptor expression, platelet spreading, or clot retraction. Additionally, IOX-2 (10\u2009mg\/kg) was injected intraperitoneally into mice to measure tail bleeding time and arterial thrombosis. IOX-2 significantly inhibited collagen-related peptide (CRP; 0.25\u2009\u03bcg\/mL) or thrombin (0.03 U\/mL)-induced platelet aggregation and ATP release dose dependently without affecting P-selectin expression and the surface levels of glycoprotein (GP)Ib\u03b1, GPVI, or \u03b1IIb\u03b23. In addition, IOX-2-treated platelets presented significantly decreased spreading on fibrinogen or collagen and clot retraction. Moreover, IOX-2 administration into mice significantly impaired the in vivo hemostatic function of platelets and arterial thrombus formation without affecting the number of circulating platelets and coagulation factors (FVIII and FIX). Further, IOX-2 significantly upregulated HIF-1\u03b1 in platelets, decreased ROS generation, and downregulated NOX1 expression. Finally, IOX-2 increased the phosphorylation level of VASP (Ser157\/239), and inhibited the phosphorylation of p38 (Thr180\/Tyr182), ERK1\/2 (Thr202\/Tyr204), AKT (Thr308\/Ser473), and PKC\u03b4 (Thr505) in CRP- or thrombin-stimulated platelets. In conclusion, inhibition of HIF prolyl-hydroxylase modulates platelet function and arterial thrombus formation, possibly through upregulation of HIF-1\u03b1 expression and subsequent inhibition of ROS generation, indicating that HIF-1\u03b1 might be a novel target for the treatment of thrombotic disorders.<\/jats:p>","DOI":"10.1055\/a-1837-7797","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T23:28:25Z","timestamp":1651102105000},"page":"1693-1705","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of Hypoxia-Inducible Factor Prolyl-Hydroxylase Modulates Platelet Function"],"prefix":"10.1055","volume":"122","author":[{"given":"Wei","family":"Gu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqian","family":"Qi","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, China"},{"name":"Collaborative Innovation Center of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, China"},{"name":"Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China"},{"name":"State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Ding","sequence":"additional","affiliation":[{"name":"Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Qiao","sequence":"additional","affiliation":[{"name":"Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7560-7195","authenticated-orcid":false,"given":"Yue","family":"Han","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, China"},{"name":"Collaborative Innovation Center of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, China"},{"name":"Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China"},{"name":"State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 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