Expression and activation of the farnesoid X receptor in the vasculature.
The farnesoid X receptor/bile acid receptor (FXR) is a recently discovered member of the nuclear hormone superfamily. FXR ligands have been proposed as targets in cardiovascular disease, regulating cholesterol metabolism and bile acid transport and metabolism in the liver and gastrointestinal tract. When we used a human cardiovascular tissue array, we found that FXR is expressed in a variety of normal and pathological human tissue. Particularly high levels of FXR were found in the vasculature and in a number of different metastatic cancers, as well as the previously identified target tissues of the liver, small intestine, and kidney. In vitro, FXR is present in rat and human vascular smooth muscle cells. When treated with a range of FXR ligands, vascular smooth muscle cells undergo apoptosis in a manner that correlates with the ligands' ability to activate FXR. Furthermore, FXR activators induce mRNA for the FXR target genes, phospholipid transfer protein, and the small heterodimer partner. FXR therefore is a functional protein in the vasculature that may provide a direct target for the treatment of proliferative and dyslipidaemic diseases.
Bishop-Bailey
David
D
Cardiac, Vascular, and Inflammation Research, William Harvey Research Institute, Barts and the London, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom. d.bishop-bailey@qmul.ac.uk
Walsh
Desmond T
DT
Warner
Timothy D
TD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated