{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:54:09Z","timestamp":1787018049444,"version":"build-2736575974"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2012,10,26]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>The recently discovered chemokine CXC motif ligand 16 (CXCL16) is highly expressed in atherosclerotic lesions and is a potential pathogenic mediator in coronary artery disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>The aim of this study was to test the role of CXCL16 on platelet activation and vascular adhesion, as well as the underlying mechanism and signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Reverse-transcriptase polymerase chain reaction, Western blotting, confocal microscopy, and flow cytometry revealed that CXCL16-specific receptor, CXC motif receptor 6, is highly expressed in platelets. According to flow cytometry and confocal microscopy, stimulation of platelets with CXCL16 induced platelet degranulation, integrin \u03b1\n                      <jats:sub>IIb<\/jats:sub>\n                      \u03b2\n                      <jats:sub>3<\/jats:sub>\n                      activation, and shape change. CXCL16 increased Akt phosphorylation (Thr\n                      <jats:sup>308<\/jats:sup>\n                      \/Ser\n                      <jats:sup>473<\/jats:sup>\n                      ), an effect abrogated by phosphatidylinositide 3-kinase inhibitors wortmannin (100 nmol\/L) and LY294002 (25 \u00b5mol\/L). The phosphatidylinositide 3-kinase inhibitors and Akt inhibitor SH-6 (20 \u00b5mol\/L) further diminished CXCL16-induced platelet activation. CXCL16-mediated platelet degranulation, integrin \u03b1\n                      <jats:sub>IIb<\/jats:sub>\n                      \u03b2\n                      <jats:sub>3<\/jats:sub>\n                      activation, and Akt phosphorylation were blunted in platelets lacking CXCL16-specific receptor CXC motif receptor 6. CXCL16-induced platelet activation was abrogated in Akt1- or Akt2-deficient platelets. CXCL16 enhanced platelet adhesion to endothelium in vitro after high arterial shear stress (2000\n                      <jats:sup>\u2212s<\/jats:sup>\n                      ) and to injured vascular wall in vivo after carotid ligation. CXCL16-induced stimulation of platelet adhesion again was prevented by phosphatidylinositide 3-kinase and Akt inhibitors. Apyrase and antagonists of platelet purinergic receptors P\n                      <jats:sub>2<\/jats:sub>\n                      Y\n                      <jats:sub>1<\/jats:sub>\n                      (MRS2179, 100 \u00b5mol\/L) and especially P\n                      <jats:sub>2<\/jats:sub>\n                      Y\n                      <jats:sub>12<\/jats:sub>\n                      (Cangrelor, 10 \u00b5mol\/L) blunted CXCL16-triggered platelet activation as well as CXCL16-induced platelet adhesion under high arterial shear stress in vitro and after carotid ligation in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>The inflammatory chemokine CXCL16 triggers platelet activation and adhesion via CXC motif receptor 6\u2013dependent phosphatidylinositide 3-kinase\/Akt signaling and paracrine activation, suggesting a decisive role for CXCL16 in linking vascular inflammation and thrombo-occlusive diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.112.276444","type":"journal-article","created":{"date-parts":[[2012,8,28]],"date-time":"2012-08-28T00:01:29Z","timestamp":1346112089000},"page":"1297-1307","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":124,"title":["The Inflammatory Chemokine CXC Motif Ligand 16 Triggers Platelet Activation and Adhesion Via CXC Motif Receptor 6\u2013Dependent Phosphatidylinositide 3-Kinase\/Akt Signaling"],"prefix":"10.1161","volume":"111","author":[{"given":"Oliver","family":"Borst","sequence":"first","affiliation":[{"name":"From the Medizinische Klinik III, Department of Cardiology and Cardiovascular Medicine (O.B., T.S., K.S., P.S., A.E.M., M.G.) and Department of Physiology (O.B., P.M., S.G., E-M.S., E.S., S.T.T., F.L.), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"M\u00fcnzer","sequence":"additional","affiliation":[{"name":"From the Medizinische Klinik III, Department of Cardiology and Cardiovascular Medicine (O.B., T.S., K.S., P.S., A.E.M., M.G.) and Department of Physiology (O.B., P.M., S.G., E-M.S., E.S., S.T.T., F.L.), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergios","family":"Gatidis","sequence":"additional","affiliation":[{"name":"From the Medizinische Klinik III, Department of Cardiology and Cardiovascular Medicine (O.B., T.S., K.S., P.S., A.E.M., M.G.) and Department of Physiology (O.B., P.M., S.G., E-M.S., E.S., S.T.T., F.L.), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva-Maria","family":"Schmidt","sequence":"additional","affiliation":[{"name":"From the Medizinische Klinik III, Department of Cardiology and Cardiovascular Medicine (O.B., T.S., K.S., P.S., A.E.M., M.G.) and Department of Physiology (O.B., P.M., S.G., E-M.S., E.S., S.T.T., F.L.), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Sch\u00f6nberger","sequence":"additional","affiliation":[{"name":"From the Medizinische Klinik III, Department of Cardiology and Cardiovascular Medicine (O.B., T.S., K.S., P.S., A.E.M., M.G.) and Department of Physiology (O.B., P.M., S.G., E-M.S., E.S., S.T.T., F.L.), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evi","family":"Schmid","sequence":"additional","affiliation":[{"name":"From the Medizinische Klinik III, Department of Cardiology and Cardiovascular Medicine (O.B., T.S., K.S., P.S., A.E.M., M.G.) and Department of Physiology (O.B., P.M., S.G., E-M.S., E.S., S.T.T., F.L.), University 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