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. 2008:2008:825970.
doi: 10.1155/2008/825970.

A Role for PPARbeta/delta in Ocular Angiogenesis

David Bishop-Bailey  1
Affiliations

A Role for PPARbeta/delta in Ocular Angiogenesis

David Bishop-Bailey. PPAR Res. 2008.

Abstract

The uses of highly selective PPARbeta/delta ligands and PPARbeta/delta knockout mice have shown a direct ability of PPARbeta/delta to regulate angiogenesis in vitro and in vivo in animal models. PPARbeta/delta ligands induce the proangiogenic growth factor VEGF in many cells and tissues, though its actions in the eye are not known. However, virtually, all tissue components of the eye express PPARbeta/delta. Both angiogenesis and in particular VEGF are not only critical for the development of the retina, but they are also a central component in many common pathologies of the eye, including diabetic retinopathy and age-related macular degeneration, the most common causes of blindness in the Western world. This review, therefore, will discuss the recent evidence of PPARbeta/delta-mediated angiogenesis and VEGF release in the context of ocular disorders.

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Figures

Figure 1
Figure 1
Proangiogenic/prosurvival pathways of PPARβ/δ in endothelial cells. PPARβ/δ is expressed in endothelial cells. PPARβ/δ activation induces (solid line) the expression of VEGF and its receptor Flt-1, matrix metalloproteinase (MMP)-9, thrombospondin and its receptor CD36, the chloride intracellular channel protein (CLIC)-4, the cell cycle inhibitor p57kip2, and the antiapoptotic protein 14-3-3α. In contrast, the cellular retinol binding protein-1 is decreased (dashed line) by PPARβ/δ activation. For those interested, a complex transcriptional map of the potential role of PPARβ/δ as a hub node in tumour angiogenesis has recently also been formed as detailed in [32].
Figure 2
Figure 2
Anti-inflammatory/anticoagulation pathways of PPARβ/δ. PPARβ/δ activation in endothelial cells reduces NFκB activation and the induction of vascular cell adhesion molecule (VCAM)-1, and monocyte chemoattractant protein (MCP)-1, along with the release of tissue factor. PPARβ/δ is expressed in platelets and monocytes/macrophages. PPARβ/δ ligands reduce platelet aggregation via a rapid nongenomic mechanism. In macrophages, PPARβ/δ ligands release the transcriptional corepressor BCL-6 from its complex with PPARβ/δ. Free BCL-6 suppresses the release of MCP-1, MCP-3, and IL-1β.
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