Transcriptional repression of atherogenic inflammation: modulation by PPARdelta Export

@article{Lee:2003p323, abstract = {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) gamma promotes lipid uptake and efflux in these atherogenic cells. In contrast, we found that the closely related receptor PPARdelta controls the inflammatory status of the macrophage. Deletion of PPARdelta 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 PPARdelta controls an inflammatory switch through its association and disassociation with transcriptional repressors. PPARdelta and its ligands may thus serve as therapeutic targets to attenuate inflammation and slow the progression of atherosclerosis.}, author = {Lee, Chih H. and Chawla, Ajay and Urbiztondo, Ned and Liao, Debbie and Boisvert, William A. and Evans, Ronald M. and Curtiss, Linda K.}, citeulike-article-id = {3046182}, citeulike-linkout-0 = {http://www.sciencemag.org/cgi/content/full/302/5644/453}, citeulike-linkout-1 = {http://dx.doi.org/10.1126/science.1087344}, doi = {10.1126/science.1087344}, journal = {Science}, keywords = {9, and, animals, arteriosclerosis, bone, c-bcl-6, c57bl, ccl2, cells, chemokine, cholesterol, cytoplasmic, disease, dna-binding, expression, factors, file-import-08-07-27, foam, gene, genetic, inbred, inflammation, interleukin-1, ligands, lipid, lipids, macrophages, marrow, matrix, metabolism, metalloproteinase, mice, nuclear, progression, proteins, proto-oncogene, receptors, regulation, repressor, signal, transcription, transduction, transplantation}, local-url = {file://localhost/Users/ken/Documents/Papers/2003/Lee/Science\%202003\%20Lee.pdf}, month = {Oct}, number = {5644}, pages = {453--7}, posted-at = {2008-07-27 14:46:00}, priority = {2}, title = {Transcriptional repression of atherogenic inflammation: modulation by PPARdelta}, url = {http://dx.doi.org/10.1126/science.1087344}, volume = {302}, year = {2003} }

TY - JOUR ID - Lee:2003p323 L3 - citeulike-article-id:3046182 N2 - 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) gamma promotes lipid uptake and efflux in these atherogenic cells. In contrast, we found that the closely related receptor PPARdelta controls the inflammatory status of the macrophage. Deletion of PPARdelta 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 PPARdelta controls an inflammatory switch through its association and disassociation with transcriptional repressors. PPARdelta and its ligands may thus serve as therapeutic targets to attenuate inflammation and slow the progression of atherosclerosis. IS - 5644 JF - Science EP - 7 TI - Transcriptional repression of atherogenic inflammation: modulation by PPARdelta VL - 302 SP - 453 KW - 9 KW - and KW - animals KW - arteriosclerosis KW - bone KW - c-bcl-6 KW - c57bl KW - ccl2 KW - cells KW - chemokine KW - cholesterol KW - cytoplasmic KW - disease KW - dna-binding KW - expression KW - factors KW - file-import-08-07-27 KW - foam KW - gene KW - genetic KW - inbred KW - inflammation KW - interleukin-1 KW - ligands KW - lipid KW - lipids KW - macrophages KW - marrow KW - matrix KW - metabolism KW - metalloproteinase KW - mice KW - nuclear KW - progression KW - proteins KW - proto-oncogene KW - receptors KW - regulation KW - repressor KW - signal KW - transcription KW - transduction KW - transplantation AU - Lee, Chih AU - Chawla, Ajay AU - Urbiztondo, Ned AU - Liao, Debbie AU - Boisvert, William AU - Evans, Ronald AU - Curtiss, Linda PY - 2003/Oct// UR - http://dx.doi.org/10.1126/science.1087344 ER -