{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:04:10Z","timestamp":1792062250927,"version":"4.4.0"},"reference-count":23,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5644","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2003,10,17]]},"abstract":"<jats:p>The formation of an atherosclerotic lesion is mediated by lipid-laden macrophages (foam cells), which also establish chronic inflammation associated with lesion progression. The peroxisome proliferator-activated receptor (PPAR) \u03b3 promotes lipid uptake and efflux in these atherogenic cells. In contrast, we found that the closely related receptor PPAR\u03b4 controls the inflammatory status of the macrophage. Deletion of PPAR\u03b4 from foam cells increased the availability of inflammatory suppressors, which in turn reduced atherosclerotic lesion area by more than 50%. We propose an unconventional ligand-dependent transcriptional pathway in which PPAR\u03b4 controls an inflammatory switch through its association and disassociation with transcriptional repressors. PPAR\u03b4 and its ligands may thus serve as therapeutic targets to attenuate inflammation and slow the progression of atherosclerosis.<\/jats:p>","DOI":"10.1126\/science.1087344","type":"journal-article","created":{"date-parts":[[2003,9,15]],"date-time":"2003-09-15T20:48:19Z","timestamp":1063658899000},"page":"453-457","source":"Crossref","is-referenced-by-count":496,"title":["Transcriptional Repression of Atherogenic Inflammation: Modulation by PPAR\u03b4"],"prefix":"10.1126","volume":"302","author":[{"given":"Chih-Hao","family":"Lee","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA."},{"name":"Vascular Medicine Research, Brigham &amp; Women's Hospital, 65 Landsdowne Street, Room 275, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Chawla","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA."},{"name":"Vascular Medicine Research, Brigham &amp; Women's Hospital, 65 Landsdowne Street, Room 275, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ned","family":"Urbiztondo","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA."},{"name":"Vascular Medicine Research, Brigham &amp; Women's Hospital, 65 Landsdowne Street, Room 275, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Liao","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA."},{"name":"Vascular Medicine Research, Brigham &amp; Women's Hospital, 65 Landsdowne Street, Room 275, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Boisvert","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA."},{"name":"Vascular Medicine Research, Brigham &amp; Women's Hospital, 65 Landsdowne Street, Room 275, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA."},{"name":"Vascular Medicine Research, Brigham &amp; Women's Hospital, 65 Landsdowne Street, Room 275, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00164-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.112059299"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182199799"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(02)00668-9"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1102-1243"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108482200"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091021198"},{"key":"e_1_3_2_9_2","unstructured":"C. H. Lee R. M. Evans unpublished data."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0337331100"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5624"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80139-2"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(98)00318-9"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/29788"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1102-1235"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5312.589"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/79749"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/83336"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1101\/gad.14.14.1810","volume":"14","year":"2000","unstructured":"K. D. Huynh, W. Fischle, E. Verdin, V. J. Bardwell, Genes Dev.14, 1810 (2000).","journal-title":"Genes Dev."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201736200"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1102-1218"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1102-1211"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00809-7"},{"key":"e_1_3_2_24_2","unstructured":"We thank J. L. Witztum C. K. Glass P. Tontonoz W. Alaynick P. Olson and R. Nofsinger for valuable comments; R. Yu M. Downes Y. Wang and W. He for reagents; I. Mehl for Q-PCR analyses; L. K. Curtiss and A. S. Black for assistance in macrophage differentiation; A. L. Dent for pGCN-BCL-6 plasmid; H.-Y. Kao for BCL-6 deletion plasmids; and E. Stevens and L. Ong for administrative assistance. R.M.E. is an investigator of the Howard Hughes Medical Institute at the Salk Institute for Biological Studies and March of Dimes Chairin Molecular and Developmental Biology. Supported by the Howard Hughes Medical Institute (R.M.E.) and NIH grant HL69474 (W.A.B.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1087344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:59:35Z","timestamp":1704837575000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1087344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10,17]]},"references-count":23,"journal-issue":{"issue":"5644","published-print":{"date-parts":[[2003,10,17]]}},"alternative-id":["10.1126\/science.1087344"],"URL":"https:\/\/doi.org\/10.1126\/science.1087344","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10,17]]}}}