A Single Treatment With a Specific Chymase Inhibitor, TY-51184, Prevents Vascular Proliferation in Canine Grafted Veins

Abstract

In this study, we evaluated whether a specific chymase inhibitor, TY-51184 (2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl]oxazole-4-carboxylicacid), prevents the vascular proliferation in canine grafted veins. In the placebo- and chymase inhibitor-treated groups, the external jugular vein was infiltrated with saline and 10 μM TY-51184, respectively, and then it was grafted to the ipsilateral carotid artery. The non-surgical dogs were used as the control group. By 28 days after grafting, the chymase and ACE activities were significantly increased in the injured arteries. TY-51184 significantly reduced the chymase activity in the grafted veins, while it did not affect the ACE activity. The intimal areas in the placebo- and TY-51184-treated groups were 3.32 ± 0.16 and 1.96 ± 0.52 mm2, respectively, and this difference was significant. The ratios of intimal area to medial area in the placebo- and TY-51184-treated groups were 66.8 ± 3.5% and 34.9 ± 9.2%, respectively, and this difference was also significant. There was a significant relationship between vascular proliferation and chymase activity, but not ACE activity. In this study, we demonstrated that a single treatment with a specific chymase inhibitor, TY-51184, could prevent the vascular proliferation in canine grafted veins. Keywords:: chymase, inhibitor, graft, vascular proliferation