A role for urotensin II in restenosis following balloon angioplasty: use of a selective UT receptor blocker

Recent studies have postulated that the vasoactive peptide urotensin II (UII) plays a role in the control of vascular remodeling by inducing smooth muscle proliferation and fibroblast-mediated collagen deposition. The present study examined the expression of UII mRNA and immunoreactivity in rat carotid arteries before and after balloon angioplasty. In addition, the effect of UT receptor blockade was assessed in this model using a selective non-peptidic UT receptor antagonist, SB-611812. In carotid arteries of uninjured rats (naïve group), there was weak expression of UII in endothelial cells and little to no expression in vascular smooth muscle cells. At day 7, there was intimal proliferation associated with pronounced expression of UII in myointimal cells. By day 14, there was extensive intimal thickening exhibiting strong expression of UII. The contralateral arteries of all groups exhibited similar UII expression to that of naïve arteries. Animals treated with methylcellulose (vehicle) for 28 days showed a significant increase in intimal thickening compared to sham operated animals. Treatment with the SB-611812 resulted in a significant 60% reduction in intima-to-media area ratio when compared to vehicle treatment (P < 0.005). These findings demonstrate upregulation of UII following balloon angioplasty, and a significant reduction in intimal lesion in response to UT receptor blockade. The present study suggests an important role for UII in the pathogenesis of restenosis following balloon angioplasty.