{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:18:25Z","timestamp":1792603105186,"version":"4.5.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,8,6]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Venous thromboembolism is associated with endothelial cell activation that contributes to the inflammation\u2010dependent activation of the coagulation system. Cellular damage is associated with the release of different species of extracellular RNA (eRNA) involved in inflammation and coagulation. TLR3 (toll\u2010like receptor 3), which recognizes (viral) single\u2010stranded or double\u2010stranded RNAs and self\u2010RNA fragments, might be the receptor of these species of eRNA during venous thromboembolism. Here, we investigate how the TLR3\/eRNA axis contributes to venous thromboembolism.<\/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              Thrombus formation and size in wild\u2010type and TLR3 deficient (\u2212\/\u2212) mice were monitored by ultrasonography after venous thrombosis induction using the ferric chloride and stasis models. Mice were treated with RNase I, with polyinosinic\u2010polycytidylic acid, a TLR3 agonist, or with RNA extracted from murine endothelial cells. Gene expression and signaling pathway activation were analyzed in HEK293T cells overexpressing TLR3 in response to eRNA or in human umbilical vein endothelial cells transfected with a small interference RNA against TLR3. Plasma clot formation on treated human umbilical vein endothelial cells was analyzed. Thrombosis exacerbated eRNA release in\u00a0vivo and increased eRNA content within the thrombus. RNase I treatment reduced thrombus size compared with vehicle\u2010treated mice (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). Polyinosinic\u2010polycytidylic acid and eRNA treatments increased thrombus size in wild\u2010type mice (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01 and\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05), but not in TLR3\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, by reinforcing neutrophil recruitment (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). Mechanistically, TLR3 activation in endothelial cells promotes CXCL5 (C\u2010X\u2010C motif chemokine 5) secretion (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and NF\u03baB (nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells) activation (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). Finally, eRNA triggered plasma clot formation in\u00a0vitro (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">We show that eRNA and TLR3 activation enhance venous thromboembolism through neutrophil recruitment possibly through secretion of CXCL5, a potent neutrophil chemoattractant.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.034492","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T10:52:27Z","timestamp":1721386347000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Extracellular RNA Induces Neutrophil Recruitment Via Toll\u2010Like Receptor 3 During Venous Thrombosis After Vascular Injury"],"prefix":"10.1161","volume":"13","author":[{"given":"Maria Y.","family":"Najem","sequence":"first","affiliation":[{"name":"Univ Brest, Inserm, UMR 1304, GETBO","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan N.","family":"Rys","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research","place":["Montr\u00e9al, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Laurance","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research","place":["Montr\u00e9al, Canada"]},{"name":"INSERM, BIGR, Universit\u00e9 de Paris and Universit\u00e9 des Antilles","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2820-8431","authenticated-orcid":false,"given":"Fran\u00e7ois\u2010Ren\u00e9","family":"Bertin","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research","place":["Montr\u00e9al, Canada"]},{"name":"The University of Queensland","place":["Gatton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1595-2528","authenticated-orcid":false,"given":"Virginie","family":"Gourdou\u2010Latyszenok","sequence":"additional","affiliation":[{"name":"Univ Brest, Inserm, UMR 1304, GETBO","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5761-8480","authenticated-orcid":false,"given":"L\u00e9na\u00efck","family":"Gourhant","sequence":"additional","affiliation":[{"name":"Univ Brest, Inserm, UMR 1304, GETBO","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauriane","family":"Le Gall","sequence":"additional","affiliation":[{"name":"Univ Brest, Inserm, UMR 1304, GETBO","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5621-074X","authenticated-orcid":false,"given":"Rozenn","family":"Le Corre","sequence":"additional","affiliation":[{"name":"Univ Brest, Inserm, UMR 1304, GETBO","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1855-8032","authenticated-orcid":false,"given":"Francis","family":"Couturaud","sequence":"additional","affiliation":[{"name":"Univ Brest, Inserm, UMR 1304, GETBO","place":["Brest, France"]},{"name":"CHU Brest","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Blostein","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research","place":["Montr\u00e9al, Canada"]},{"name":"Sir Mortimer B. 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