Vascular Protein Receptor May Protect Against Cardiovascular Disease

The protein called pregnane X receptor (PXR) has been found to be active in vascular tissue where it upregulates drug metabolism, transport, and antioxidant genes to protect the vasculature from both endogenous and exogenous damage.

PXR is a nuclear receptor whose primary function is to sense the presence of foreign toxic substances and in response upregulate the expression of proteins involved in the detoxification and clearance of these substances from the body. PXR belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain.

In a study published in the March 15, 2012, issue of the journal Cardiovascular Research, a team of British investigators reported that they had detected PXR in primary human and rat aortic endothelial and smooth muscle cells and in blood vessels including the human and rat aorta. Activation of aortic PXR by classical agonists had several protective effects: increased xenobiotic metabolism demonstrated by bioactivation of the pro-drug clopidogrel, which reduced adenosine diphosphate-induced platelet aggregation; increased expression of multidrug resistance protein 1, mediating chemical efflux from the vasculature; and protection from reactive oxygen species-mediated cell death.

“We have known for a long time that this protein has an important role sorting out waste products in the liver--now we believe it could have an important role in protecting the body against cardiovascular disease,” said senior author Dr. David Bishop-Bailey, lecturer on cardiovascular and inflammatory disorders at the William Harvey Research Institute (London, United Kingdom). “Since blood travels everywhere in the body, PXR has the potential to provide protection not just through its actions in the liver, but anywhere in the entire body. If we can work out how to manipulate PXR to turn on detoxification and antioxidant pathways in blood vessels, we may be a step closer to preventing our nation's biggest killer.”

Related Links:
William Harvey Research Institute