{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T08:04:06Z","timestamp":1775549046143,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000964","name":"Arthritis National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000964","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/06868\u20101"],"award-info":[{"award-number":["2022\/06868\u20101"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08AR080205"],"award-info":[{"award-number":["K08AR080205"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL134846"],"award-info":[{"award-number":["R01HL134846"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>ATP is released from platelets through both degranulation and pannexin\u20101 (PANX1) channels. ATP then activates P2X receptors to amplify platelet activation via calcium\u2010dependent signaling. The objective of this study was to evaluate the role of platelet PANX1 channels in the pathophysiology of antiphospholipid syndrome (APS), an acquired thromboinflammatory disorder characterized by platelet\u2010activating antiphospholipid antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Extracellular ATP release was measured in platelets isolated from patients with persistently positive antiphospholipid antibodies (n\u00a0=\u00a036), patients with systemic lupus erythematosus (n\u00a0=\u00a010), and healthy controls (n\u00a0=\u00a016). In some assays, purified platelets were pretreated with the PANX inhibitor carbenoxolone. Platelet signaling, P\u2010selectin exposure, and aggregation were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Basal ATP release was significantly higher in APS platelets than in controls (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and normalized in the presence of carbenoxolone (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03). Carbenoxolone also reduced platelet ATP release and surface P\u2010selectin expression induced by thrombin (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.002 and\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.02, respectively) and convulxin (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0001 and\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0012). Control platelets stimulated with IgG from patients with APS demonstrated enhanced phosphorylation of PANX1 at tyrosine\u2010308 (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03), which was accompanied by enhanced ATP release (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0004). APS IgG boosted ADP\u2010induced aggregation (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0011), which was reduced by carbenoxolone (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0007). The calcium chelator BAPTA\u2010AM decreased APS IgG\u2013mediated ATP release (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03), P\u2010selectin expression (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0005), and aggregation (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0007). Desensitizing P2X1 receptors with \u03b1,\u03b2\u2010MeATP decreased APS IgG\u2013induced P\u2010selectin expression (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0002) and aggregation (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PANX1 channels appear to be important mediators of platelet activation in APS. Agents that block PANX1 may restore platelet homeostasis and limit thrombosis without impairing hemostasis.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70001-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70001","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T06:50:31Z","timestamp":1764658231000},"page":"896-903","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prothrombotic Activation of Platelet Pannexin\u20101 Channels in Antiphospholipid Syndrome"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8778-4658","authenticated-orcid":false,"given":"Bruna","family":"de Moraes Mazetto Fonseca","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"},{"name":"School of Medical Sciences, University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8991-5041","authenticated-orcid":false,"given":"Somanathapura K.","family":"NaveenKumar","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srilakshmi","family":"Yalavarthi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavya","family":"Sugur","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thalia G.","family":"Newman","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire K.","family":"Hoy","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyrus","family":"Sarosh","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan K.","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajay","family":"Tambralli","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline A.","family":"Madison","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6721-7755","authenticated-orcid":false,"given":"Yu","family":"Zuo","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7908-9073","authenticated-orcid":false,"given":"Fernanda A.","family":"Orsi","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Medical Sciences, University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Holinstat","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Michigan Medical School  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0995-9771","authenticated-orcid":false,"given":"Jason S.","family":"Knight","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine University of Michigan  Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2021-069717"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15724"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.123.318978"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.113.008029"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2015.04.011"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-11-0673"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.07.009"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23095059"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2021.1902971"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1217366"},{"issue":"3","key":"e_1_2_6_12_1","first-page":"1296","article-title":"Pannexin1 channel\u2010mediated inflammation in acute ischemic stroke","volume":"15","author":"Huang Y","year":"2024","journal-title":"Aging Dis"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023022097"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00070.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030144"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.084673"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.70001","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T07:16:08Z","timestamp":1775546168000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.70001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,29]]},"references-count":15,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/art.70001"],"URL":"https:\/\/doi.org\/10.1002\/art.70001","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,29]]},"assertion":[{"value":"2025-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}