{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:33:18Z","timestamp":1790469198544,"version":"4.1.0"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,2,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Antiplatelet therapy with aspirin (acetylsalicylic acid [ASA]) is less efficient in some coronary patients, which increases their risk of developing thrombosis. Elevated blood levels of thromboinflammatory mediators, like soluble CD40L (sCD40L), may explain such variabilities. We hypothesized that in the presence of elevated levels of\n              <jats:styled-content style=\"fixed-case\">sCD<\/jats:styled-content>\n              40L, the efficacy of\n              <jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>\n              may vary and aimed to determine the effects of\n              <jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>\n              on\n              <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n              40L signaling and aggregation of platelets.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The effects of\n              <jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>\n              on\n              <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n              40L\u2010treated human platelets, in response to suboptimal concentrations of collagen or thrombin, were assessed at levels of aggregation, thromboxane A\n              <jats:sub>2<\/jats:sub>\n              secretion, and phosphorylation of p38 mitogen\u2010activated protein kinase, nuclear factor kappa B, transforming growth factor\u2010\u03b2\u2013activated kinase 1, and myosin light chain.\n              <jats:styled-content style=\"fixed-case\">sCD<\/jats:styled-content>\n              40L significantly elevated thromboxane A\n              <jats:sub>2<\/jats:sub>\n              secretion in platelets in response to suboptimal doses of collagen and thrombin, which was reversed by\n              <jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>\n              .\n              <jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>\n              did not inhibit the phosphorylation of p38 mitogen\u2010activated protein kinase, nuclear factor kappa B, and transforming growth factor\u2010\u03b2\u2013activated kinase 1, with\n              <jats:styled-content style=\"fixed-case\">sCD<\/jats:styled-content>\n              40L stimulation alone or with platelet agonists.\n              <jats:styled-content style=\"fixed-case\">sCD<\/jats:styled-content>\n              40L potentiated platelet aggregation, an effect completely reversed and partially reduced by\n              <jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>\n              in response to a suboptimal dose of collagen and thrombin, respectively. The effects of\n              <jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>\n              in\n              <jats:styled-content style=\"fixed-case\">sCD<\/jats:styled-content>\n              40L\u2010treated platelets with collagen were related to inhibition of platelet shape change and myosin light chain phosphorylation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>\n              does not affect platelet\n              <jats:styled-content style=\"fixed-case\">sCD<\/jats:styled-content>\n              40L signaling but prevents its effect on thromboxane A\n              <jats:sub>2<\/jats:sub>\n              secretion and platelet aggregation in response to collagen, via a mechanism implying inhibition of myosin light chain. Targeting the sCD40L axis in platelets may have a therapeutic potential in patients with elevated levels of\n              <jats:styled-content style=\"fixed-case\">sCD<\/jats:styled-content>\n              40L and who are nonresponsive or less responsive to ASA.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.013396","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T11:12:30Z","timestamp":1580728350000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Aspirin Reduces the Potentiating Effect of CD40L on Platelet Aggregation via Inhibition of Myosin Light Chain"],"prefix":"10.1161","volume":"9","author":[{"given":"Kevin","family":"Kojok","sequence":"first","affiliation":[{"name":"The Laboratory of Thrombosis and Hemostasis Research Centre Montreal Heart Institute Montreal Quebec Canada"},{"name":"Faculty of Medicine Universit\u00e9 de Montr\u00e9al 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