PPARs in atherosclerosis: the clot thickens
Antonio Castrillo, Peter Tontonoz
Antonio Castrillo, Peter Tontonoz
Published December 1, 2004
Citation Information: J Clin Invest. 2004;114(11):1538-1540. https://doi.org/10.1172/JCI23705.
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Commentary

PPARs in atherosclerosis: the clot thickens

Abstract

Cardiovascular disease is the leading cause of morbidity and mortality in Western countries. Previous studies have highlighted the beneficial effects of PPARĪ³ activators on cardiovascular disease; however, the role of other PPAR family members in atherosclerosis is less clear. A report in this issue of the JCI expands our understanding of PPARs in vascular biology and highlights the potential use of multiple PPAR agonists to limit lipid accumulation in macrophages.

Authors

Antonio Castrillo, Peter Tontonoz

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Figure 1

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PPAR signaling pathways influence macrophage gene expression and foam-ce...
PPAR signaling pathways influence macrophage gene expression and foam-cell formation. Ligand activation of PPARα and PPARγ, but not PPARβ/δ, inhibits the development of atherosclerosis in LDLR_/_ mice. Both systemic and local mechanisms might contribute to these beneficial effects. Previous studies have suggested that PPARα and PPARγ increase LXRα expression in macrophages and promote expression of ABCA1, which mediates cholesterol efflux to apoAI. Results from the study in this issue by Li et al. (15) suggest that PPARγ may also inhibit cholesterol accumulation in macrophages through direct regulation of ABCG1, which has been implicated in cholesterol efflux to HDL. Activation of each of the PPARs with selective agonists also inhibits the expression of inflammatory markers in the artery wall. These findings reinforce potential use of PPAR agonists as antiatherosclerotic therapies. PTLP, phospholipid transfer protein.