Fig 4.

Metabolic and vascular effects of FXR. FXR heterodimerizes with RXR. The FXR/RXR heterodimer binds to FXR-responsive elements in the promoters of target genes. Following a ligand-induced activation, FXR induces the expression of genes encoding proteins involved in lipogenesis, lipoprotein clearance and glucose metabolism. In addition, FXR activation and sumoylation in macrophages stabilizes the nuclear co-repressor NCoR on NF-κB responsive element inhibiting the expression of inflammatory genes in macrophages, suppresses cell proliferation and migration and increases reverse cholesterol transport in VSMCs and endothelial cells. LDL-R, low-density lipoprotein receptor; VLDL, very low-density lipoprotein; IL-1β, interleukin 1β; IL-6, interleukin 6; TNF-α, tumour necrosis factor α; PLTP, phospholipid transfer protein; ATR-, angiotensin type 2 receptor; NO, nitric oxide and ET-1, endothelin 1.