title: The Urotensin II System and Carotid Atherosclerosis: A Role in Vascular Calcification.
abstract: OBJECTIVE
  The aims of the present study were to determine the expression of urotensin II (UII), urotensin-II related peptide (URP), and their receptor (UT) in stable and unstable carotid atherosclerosis, and determine the effects of UII on human aortic smooth muscle cell (SMCs) calcification.
  
  
  RESULTS
  We examined UII, URP, and UT protein expression in 88 carotid endarterectomy specimens using immunohistochemistry. Expression of UII, URP, and UT was more evident in unstable compared to stable plaques (P < 0.05). Multivariate Spearman correlation analyses revealed significant positive correlations between UII, URP and UT overall staining and presence of calcification, severity of stenosis and inflammation (P < 0.05). Subjects undergoing carotid endarterectomy had significantly higher plasma UII levels, as assessed by ELISA, when compared with normolipidemic healthy control subjects (P < 0.05). Incubation of human aortic SMCs cultured in phosphate media with varying concentrations of UII resulted in a significant increase in calcium deposition and alkaline phosphatase activity. UII also significantly increased β-catenin translocation and expression of ALPL, BMP2, ON, and SOX9 (P < 0.05). Incubation of cells with phosphate medium alone increased the expression of the pre-UT and mature UT (P < 0.01), and addition of UII had a synergistic effect on pre-UT protein expression (P < 0.001) compared to phosphate medium alone.
  
  
  CONCLUSIONS
  Upregulation of UII, URP, and UT in unstable carotid endarterectomy plaques and plasma, and the stimulatory effect of UII on vascular smooth muscle cell calcification suggest that the UII system may play a role in the pathogenesis of vascular calcification and stability of atherosclerosis.
authors.affiliation: Cardiology, McGill University Health Center Montreal, QC, Canada.
authors.forename: Isabella
authors.initials: I
authors.lastname: Albanese
authors.affiliation: Cardiology, McGill University Health Center Montreal, QC, Canada.
authors.forename: Stella S
authors.initials: SS
authors.lastname: Daskalopoulou
authors.affiliation: Cardiology, McGill University Health Center Montreal, QC, Canada.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Cardiology, McGill University Health Center Montreal, QC, Canada.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: You
authors.affiliation: Cardiology, McGill University Health Center Montreal, QC, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
authors.affiliation: Cardiology, College of Medicine, Mohammed Bin Rashid University Dubai, UAE.
authors.forename: Alawi
authors.initials: A
authors.lastname: Alsheikh-Ali
authors.affiliation: Cardiology, McGill University Health Center Montreal, QC, Canada.
authors.forename: Adel G
authors.initials: AG
authors.lastname: Schwertani
keywords: UII; URP; UT; calcium; immunohistochemistry; smooth muscle cells; urotensin II; urotensin II-related peptide