Peroxisome Proliferator-Activated Receptor β/δ Goes Vascular

David Bishop-Bailey

doi:10.1161/circresaha.107.170233

Abstract

See related article, pages 193–200 Peroxisome proliferator-activated receptor (PPAR)s are a family of 3 (PPARα, -β/δ, and -γ) nuclear receptor/ligand-activated transcription factors that work in concert as heterodimers with the retinoid X receptors.1 In recent years, there has been great scientific and clinical interest in the actions of PPARα and PPARγ because they are the molecular targets for the clinically used lipid-lowering fibrates and insulin-sensitizing thiazolidinedione classes of drugs, respectively.2 Until recently, very little has been known about the cellular roles of PPARδ, even though it is by far the most ubiquitously expressed of the PPAR receptors.1,3 The recent development of highly selective ligands and PPARβ/δ knockout and transgenic mice, however, have now implicated roles for PPARβ/δ in adipose tissue formation, metabolism, wound healing, brain development, placental function, colorectal carcinogenesis, and skeletal muscle function.4–6 PPARβ/δ ligands appear highly effective in regulating lipid metabolism, particularly in skeletal muscle,7,8 and are currently in phase II clinical trials for treatment of dyslipidemia, aimed particularly at individuals with low HDL levels. …

Highlights

All of the Peroxisome proliferator-activated receptor (PPAR), appear to be able to target aspects of the metabolic syndrome.[6]
There has been an increased interest in the direct roles of PPAR␤/␦ in vascular cells. This PPAR␤/␦–BCL-6 interaction, originally described in monocytes, has been shown in vascular endothelial cells to regulate the inhibition of tumor necrosis factor ␣–induced adhesion molecule expression.[12,13]
PPAR␤/␦ appears to play an important role in inducing endothelial cell angiogenesis[14,15,16] and the development of tumor vasculature.[15,16]

Summary

Introduction

All of the PPARs, appear to be able to target aspects of the metabolic syndrome.[6]. Where PPAR␤/␦ protein has been suppressed by small interfering RNA or knocked out altogether, because there is no longer any endogenous PPAR␤/␦ available to bind and inhibit the actions of BCL-6.

Results

Conclusion