{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:52:40Z","timestamp":1790419960721,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            Oxidative stress contributes to the pathogenesis of many diseases, including atherosclerosis and sepsis. We have previously described a novel class of therapeutic compounds with antioxidant and antiinflammatory properties. However, at present, the intracellular targets of these compounds have not been identified. The purpose of this study was to elucidate the mechanism by which 2 structurally-related antioxidants (AGI-1067 and AGI-1095) inhibit LPS induction of tissue factor (TF) expression in human monocytic cells and endothelial cells.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We found that succinobucol (AGI-1067) and AGI-1095 inhibited LPS induction of TF expression in both monocytic cells and endothelial cells. These compounds also reduced LPS induction of nuclear AP-1 and expression of Egr-1 without affecting nuclear translocation of NF-\u03baB. Importantly, these antioxidants inhibited LPS activation of the redox-sensitive kinase, apoptosis signal-regulating kinase-1 (ASK1) and the mitogen-activated protein kinases (MAPKs) p38, ERK1\/2, and JNK1\/2.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            AGI-1067 and AGI-1095 inhibit TF gene expression in both monocytic cells and endothelial cells through a mechanism that involves the inhibition of the redox-sensitive MAP3K, ASK1. These compounds selectively reduce the activation\/induction of MAPK, AP-1, and Egr-1 without affecting NF-\u03baB nuclear translocation.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.107.143552","type":"journal-article","created":{"date-parts":[[2007,6,9]],"date-time":"2007-06-09T04:49:40Z","timestamp":1181364580000},"page":"1857-1863","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["A Novel Class of Antioxidants Inhibit LPS Induction of Tissue Factor by Selective Inhibition of the Activation of ASK1 and MAP Kinases"],"prefix":"10.1161","volume":"27","author":[{"given":"James P.","family":"Luyendyk","sequence":"first","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Daniel","family":"Piper","sequence":"additional","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tencati","sequence":"additional","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Veera","family":"Reddy","sequence":"additional","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Holscher","sequence":"additional","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayraz","family":"Luchoomun","sequence":"additional","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilin","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Min","sequence":"additional","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Kunsch","sequence":"additional","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Mackman","sequence":"additional","affiliation":[{"name":"From the Department of Immunology (J.P.L., M.T., K.V.R., T.H., N.M.), The Scripps Research Institute, La Jolla, Calif; AtheroGenics Inc (J.D.P., J.L., X.C., C.K.), Atlanta, Ga; and the Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology (R.Z., W.M.), Yale University School of Medicine, New Haven, Conn."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2004.01.020"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.01085.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.20.10.2175"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000137822.39831.f1"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-000-0094-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.059733"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.080804"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.048132"},{"key":"e_1_3_3_9_2","unstructured":"Tardif JC Gregoire J L\u2019Allier PL Ibrahim R Anderson TJ Reeves F Title LM Schampaert E Lemay M Lesperance J Scott R Guertin MC Brennan ML Hazen SL Bertrand OF for the CART-2 Investigators. 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