{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:43:56Z","timestamp":1788414236913,"version":"build-2803163510"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>\n              Platelet activation by stimulatory factors leads to an increase in intracellular calcium concentration ([Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              ), which is essential for almost all platelet functions. Modulation of Ca\n              <jats:sup>2+<\/jats:sup>\n              influx and [Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              in platelets has been emerging as a possible strategy for preventing and treating platelet-dependent thrombosis. Voltage-gated potassium 1.3 channels (Kv1.3) are highly expressed in platelets and able to regulate agonist-evoked [Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              increase. However, the role of Kv1.3 channels in regulating platelet functions and thrombosis has not yet been elucidated. In addition, it is difficult to obtain a specific blocker for this channel, since Kv1.3 shares identical drug-binding sites with other K\n              <jats:sup>+<\/jats:sup>\n              channels. Here, we investigate whether specific blockade of Kv1.3 channels by monoclonal antibodies affects platelet functions and thrombosis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              In this study, we produced the anti-Kv1.3 monoclonal antibody 6E12#15, which could specifically recognize both human and mouse Kv1.3 proteins and sufficiently block Kv1.3 channel currents. We found Kv1.3 blockade by 6E12#15 inhibited platelet aggregation, adhesion, and activation upon agonist stimulation. In vivo treatment with 6E12#15 alleviated thrombus formation in a mesenteric arteriole thrombosis mouse model and protected mice from collagen\/epinephrine-induced pulmonary thromboembolism. Furthermore, we observed Kv1.3 regulated platelet functions by modulating Ca\n              <jats:sup>2+<\/jats:sup>\n              influx and [Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              elevation, and that this is mediated in part by P2X\n              <jats:sub>1<\/jats:sub>\n              . Interestingly,\n              <jats:italic>Kv1.3<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice showed impaired platelet aggregation while displayed no abnormalities in in vivo thrombus formation. This phenomenon was related to more megakaryocytes and platelets produced in\n              <jats:italic>Kv1.3<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice compared with wild-type mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              We showed specific inhibition of Kv1.3 by the novel monoclonal antibody 6E12#15 suppressed platelet functions and platelet-dependent thrombosis through modulating platelet [Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              elevation. These results indicate that Kv1.3 could act as a promising therapeutic target for antiplatelet therapies.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.120.314278","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T09:03:05Z","timestamp":1597309385000},"page":"2360-2375","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Role of Kv1.3 Channels in Platelet Functions and Thrombus Formation"],"prefix":"10.1161","volume":"40","author":[{"given":"Cheng","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (C.F., M.G., S.H., Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, China (X.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Wendy","family":"Wang","sequence":"additional","affiliation":[{"name":"Yale School of Public Health, New Haven, CT (W.W.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhu","family":"Li","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (W.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (C.F., M.G., S.H., Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (C.F., M.G., S.H., Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3253-7078","authenticated-orcid":true,"given":"Zhaohui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (C.F., M.G., S.H., Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4919-9896","authenticated-orcid":true,"given":"Kun","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science 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