Journal Article10.1126/SCIENCE.1087344
Transcriptional Repression of Atherogenic Inflammation: Modulation by PPARδ
TL;DR: An unconventional ligand-dependent transcriptional pathway is proposed in which PPARδ controls an inflammatory switch through its association and disassociation with transcriptional repressors and may thus serve as therapeutic targets to attenuate inflammation and slow the progression of atherosclerosis.
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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) γ promotes lipid uptake and efflux in these atherogenic cells In contrast, we found that the closely related receptor PPARδ controls the inflammatory status of the macrophage Deletion of PPARδ 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 PPARδ controls an inflammatory switch through its association and disassociation with transcriptional repressors PPARδ and its ligands may thus serve as therapeutic targets to attenuate inflammation and slow the progression of atherosclerosis
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TL;DR: The elucidation of key regulators of energy balance and insulin signaling have revolutionized the understanding of fat and sugar metabolism and their intimate link, and the three ‘lipidsensing’ (PPARα, PPARγ and PPARδ) exemplify this connection, regulating diverse aspects of lipid and glucose homeostasis, and serving as bonafide therapeutic targets.
International Union of Pharmacology. LXI. Peroxisome Proliferator-Activated Receptors
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TL;DR: The three peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily as discussed by the authors, which share a high degree of structural homology with all members of the superfamily, particularly in the DNA-binding domain and ligand and cofactor binding domain.
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References
Decreased lesion formation in CCR2 −/− mice reveals a role for chemokines in the initiation of atherosclerosis
TL;DR: A role for MCP-1 in the development of early atherosclerotic lesions is revealed and upregulation of this chemokine by minimally oxidized lipids is an important link between hyperlipidaemia and fatty streak formation.
2.1K
Absence of Monocyte Chemoattractant Protein-1 Reduces Atherosclerosis in Low Density Lipoprotein Receptor–Deficient Mice
Long Gu,Yoshikatsu Okada,Steven K. Clinton,Craig Gerard,Galina K. Sukhova,Peter Libby,Barrett J. Rollins +6 more
TL;DR: Monocyte chemoattractant protein-1 plays a unique and crucial role in the initiation of atherosclerosis and may provide a new therapeutic target in this disorder.
1.7K
A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport
William R. Oliver,Jennifer L. Shenk,Mike R. Snaith,Caroline S. Russell,Kelli D. Plunket,Noni L. Bodkin,Michael C. Lewis,Deborah A. Winegar,Marcos Luis Sznaidman,Millard H. Lambert,H. Eric Xu,Daniel D. Sternbach,Steven A. Kliewer,Barbara C. Hansen,Timothy M. Willson +14 more
TL;DR: The results suggest that PPARδ agonists may be effective drugs to increase reverse cholesterol transport and decrease cardiovascular disease associated with the metabolic syndrome X.
1.1K
PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation.
TL;DR: It is demonstrated that PPAR-γ is neither essential for nor substantially affects the development of the macrophage lineage both in vitro and in vivo, and that inhibitory effects on cytokine production and inflammation may be receptor independent.
Synthetic LXR ligand inhibits the development of atherosclerosis in mice
Sean B. Joseph,Elaine McKilligin,Liming Pei,Michael A. Watson,Alan R. Collins,Bryan A. Laffitte,Mingyi Chen,Grace Noh,Joanne Goodman,Graham N. Hagger,Jonathan Tran,Tim K. Tippin,Xuping Wang,Aldons J. Lusis,Willa A. Hsueh,Ronald E. Law,Jon L. Collins,Timothy M. Willson,Peter Tontonoz +18 more
TL;DR: It is demonstrated here that the nonsteroidal LXR agonist GW3965 has potent antiatherogenic activity in two different murine models, providing direct evidence for an atheroprotective effect of LXRs agonists and support their further evaluation as potential modulators of human cardiovascular disease.
1K