{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:24:18Z","timestamp":1791055458090,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2005,6,28]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Pathological aspects of atherosclerosis are well described, but gene profiles during atherosclerotic plaque progression are largely unidentified.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Microarray analysis was performed on mRNA of aortic arches of ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice fed normal chow (NC group) or Western-type diet (WD group) for 3, 4.5, and 6 months. Of 10 176 reporters, 387 were differentially (&gt;2\u00d7) expressed in at least 1 group compared with a common reference (ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            , 3- month NC group). The number of differentially expressed genes increased during plaque progression. Time-related expression clustering and functional grouping of differentially expressed genes suggested important functions for genes involved in inflammation (especially the small inducible cytokines monocyte chemoattractant protein [MCP]-1, MCP-5, macrophage inflammatory protein [MIP]-1\u03b1, MIP-1\u03b2, MIP-2, and fractalkine) and matrix degradation (cathepsin-S, matrix metalloproteinase-2\/12). Validation experiments focused on the gene cluster of small inducible cytokines. Real-time polymerase chain reaction revealed a plaque progression\u2013dependent increase in mRNA levels of MCP-1, MCP-5, MIP-1\u03b1, and MIP-1\u03b2. ELISA for MCP-1 and MCP-5 showed similar results. Immunohistochemistry for MCP-1, MCP-5, and MIP-1\u03b1 located their expression to plaque macrophages. An inhibiting antibody for MCP-1 and MCP-5 (11K2) was designed and administered to ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice for 12 weeks starting at the age of 5 or 17 weeks. 11K2 treatment reduced plaque area and macrophage and CD45\n            <jats:sup>+<\/jats:sup>\n            cell content and increased collagen content, thereby inducing a stable plaque phenotype.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Gene profiling of atherosclerotic plaque progression in ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice revealed upregulation of the gene cluster of small inducible cytokines. Further expression and in vivo validation studies showed that this gene cluster mediates plaque progression and stability.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.104.510073","type":"journal-article","created":{"date-parts":[[2005,6,21]],"date-time":"2005-06-21T00:28:18Z","timestamp":1119313698000},"page":"3443-3452","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":94,"title":["Gene Profiling in Atherosclerosis Reveals a Key Role for Small Inducible Cytokines"],"prefix":"10.1161","volume":"111","author":[{"given":"Esther","family":"Lutgens","sequence":"first","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Faber","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitty","family":"Schapira","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris T.A.","family":"Evelo","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"van Haaften","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Heeneman","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitty B.J.M.","family":"Cleutjens","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). 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Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Beckers","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Gordon","family":"Porter","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Mackay","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Rennert","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Bailly","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Jarpe","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Dolinski","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Koteliansky","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"de Fougerolles","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). Drs de Fougerolles..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat J.A.P.","family":"Daemen","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (E.L., B.F., K.S., S.H., K.B.J.M.C., A.P.B., L.B., M.J.A.P.D.) and Bioinformatics (C.T.A.E., R.v.H.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands; Incyte Corporation, Palo Alto, Calif (J.G.P.); Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia (C.R.M.); and Biogen-Idec Inc, Cambridge, Mass (P.R., V.B., M.J., B.D., V.K., T.d.F.). 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