{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:41:24Z","timestamp":1791074484178,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2006,9,19]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Heparin, used clinically as an anticoagulant, also has antiinflammatory properties and has been described to inhibit interferon (IFN)-\u03b3 responses in endothelial cells. We investigated the effects of heparin on the IFN-\u03b3\u2013inducible chemokines IP-10\/CXCL10, I-TAC\/CXCL11, and Mig\/CXCL9, which play important roles in the vascular recruitment of IFN-\u03b3\u2013producing Th1 cells through interactions with their cognate receptor, CXCR3.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Patients undergoing coronary artery bypass grafting were studied because coronary atherosclerosis is recognized as a Th1-type inflammatory disease and the subjects required systemic heparinization. Plasma levels of IP-10, I-TAC, and Mig increased immediately after heparin administration and diminished promptly after heparin antagonism with protamine. These effects were independent of detectable circulating IFN-\u03b3 or the IFN-\u03b3 inducer interleukin-12. We confirmed previous reports that heparin inhibits the IFN-\u03b3\u2013dependent production of CXCR3 chemokine ligands using atherosclerotic coronary arteries in organ culture. In addition to prolonged treatment decreasing chemokine secretion, heparin rapidly displaced membrane-associated IP-10 from cultured endothelial cells that did not express CXCR3 and reduced the IP-10\u2013dependent transendothelial migration of T helper cells under conditions of venular shear stress. Finally, heparin administration to immunodeficient mouse hosts decreased both the recruitment and accumulation of memory T cells within allogeneic human coronary arteries.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Besides inhibiting IFN-\u03b3 responses, heparin has further immunomodulatory effects by competing for binding with IP-10, I-TAC, and Mig on endothelial cells. Disruption of CXCR3\n            <jats:sup>+<\/jats:sup>\n            Th1 cell trafficking to arteriosclerotic arteries may contribute to the therapeutic efficacy of heparin in inflammatory arterial diseases, and nonanticoagulant heparin derivatives may represent a novel antiinflammatory strategy.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.106.631457","type":"journal-article","created":{"date-parts":[[2006,8,29]],"date-time":"2006-08-29T02:10:51Z","timestamp":1156817451000},"page":"1293-1300","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":55,"title":["Heparin Displaces Interferon-\u03b3\u2013Inducible Chemokines (IP-10, I-TAC, and Mig) Sequestered in the Vasculature and Inhibits the Transendothelial Migration and Arterial Recruitment of T Cells"],"prefix":"10.1161","volume":"114","author":[{"given":"Hooman","family":"Ranjbaran","sequence":"first","affiliation":[{"name":"From the Interdepartmental Program in Vascular Biology and Transplantation and the Departments of Surgery (H.R., Y.W., A.O.Y., G.T.), Pathology (T.D.M., J.S.P.), Anesthesiology (S.A.), and Dermatology (M.S.K., J.S.P.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinong","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Interdepartmental Program in Vascular Biology and Transplantation and the Departments of Surgery (H.R., Y.W., A.O.Y., G.T.), Pathology (T.D.M., J.S.P.), Anesthesiology (S.A.), and Dermatology (M.S.K., J.S.P.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Manes","sequence":"additional","affiliation":[{"name":"From the Interdepartmental Program in Vascular Biology and Transplantation and the Departments of Surgery (H.R., Y.W., A.O.Y., G.T.), Pathology (T.D.M., J.S.P.), Anesthesiology (S.A.), and Dermatology (M.S.K., J.S.P.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander O.","family":"Yakimov","sequence":"additional","affiliation":[{"name":"From the Interdepartmental Program in Vascular Biology and Transplantation and the Departments of Surgery (H.R., Y.W., A.O.Y., G.T.), Pathology (T.D.M., J.S.P.), Anesthesiology (S.A.), and Dermatology (M.S.K., J.S.P.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamsuddin","family":"Akhtar","sequence":"additional","affiliation":[{"name":"From the Interdepartmental Program in Vascular Biology and Transplantation and the Departments of Surgery (H.R., Y.W., A.O.Y., G.T.), Pathology (T.D.M., J.S.P.), Anesthesiology (S.A.), and Dermatology (M.S.K., J.S.P.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Kluger","sequence":"additional","affiliation":[{"name":"From the Interdepartmental Program in Vascular Biology and Transplantation and the Departments of Surgery (H.R., Y.W., A.O.Y., G.T.), Pathology (T.D.M., J.S.P.), Anesthesiology (S.A.), and Dermatology (M.S.K., J.S.P.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan S.","family":"Pober","sequence":"additional","affiliation":[{"name":"From the Interdepartmental Program in Vascular Biology and Transplantation and the Departments of Surgery (H.R., Y.W., A.O.Y., G.T.), Pathology (T.D.M., J.S.P.), Anesthesiology (S.A.), and Dermatology (M.S.K., J.S.P.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Tellides","sequence":"additional","affiliation":[{"name":"From the Interdepartmental Program in Vascular Biology and Transplantation and the Departments of Surgery (H.R., Y.W., A.O.Y., G.T.), Pathology (T.D.M., J.S.P.), Anesthesiology (S.A.), and Dermatology (M.S.K., J.S.P.), Yale University School of Medicine, New Haven, 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