Roles of xenobiotic receptors in vascular pathophysiology

Abstract

The pregnane X receptor (PXR) and constitutive androstane receptor (CAR), 2 closely related and liver-enriched members of the nuclear receptor superfamily, and aryl hydrocarbon receptor (AhR), a nonnuclear receptor transcription factor (TF), are major receptors/TFs regulating the expression of genes for the clearance and detoxification of xenobiotics. They are hence defined as "xenobiotic receptors". Recent studies have demonstrated that PXR, CAR and AhR also regulate the expression of key proteins involved in endobiotic responses such as the metabolic homeostasis of lipids, glucose, and bile acid, and inflammatory processes. It is suggested that the functions of PXR, CAR and AhR may be closely implicated in the pathogeneses of metabolic vascular diseases, such as hyperlipidemia, atherogenesis, and hypertension. Therefore, manipulation of the activities of these receptors may provide novel strategies for the treatment of vascular diseases. Here, we review the pathophysiological roles of PXR, CAR and AhR in the vascular system.