Urotensin II, Urotensin-Related Peptide and their Receptor in Aortic Valve Stenosis

Abstract Objectives Aortic valve stenosis (AVS) is the most common cause of surgical valve replacement worldwide. The vasoactive peptide urotensin II (UII) is upregulated in atherosclerosis and several other cardiovascular diseases, however its role in the pathogenesis of AVS remains to be determined. Here, we investigated the expression of UII, urotensin-related peptide (URP) and the urotensin receptor (UT), and the role the UII system plays in AVS. Methods Immunohistochemistry and RT-PCR were used to examine the cellular localization and mRNA expression, of UII, URP and UT in calcified and non-calcified aortic valves. Human aortic valve interstitial cells (HAVICs) were isolated from normal valves and treated with UII or URP, and changes in cell proliferation, cholesterol efflux, calcium deposition, and β-catenin translocation were assessed. Results The mRNA expression of UII, URP and UT were significantly higher in AVS patients. There was abundant presence of UII, URP and UT immunostaining in diseased compared to non-diseased valves and correlated significantly with presence of calcification (P Conclusions Together, these data suggest that the urotensin system plays a role in the pathogenesis of AVS and warrants further investigation.