Tetradecylthioacetic acid reduces stenosis development after balloon angioplasty injury of rabbit iliac arteries

Background: tetradecylthioacetic acid (TTA) is a synthetic long-chain fatty acid analogue that inhibits the oxidative modification of low-density lipo protein particles in vitro. We examined the influence of TTA on the arteria l wall response after balloon angioplasty injury in a rabbit iliac model. M ethods and results: 14 rabbits were randomized to receiving either TTA fatt y acids 800 mg daily perorally (weight 3.6 +/- 0.1 kg) or to normal diet (w eight 3.5 +/- 0.5 kg, P = NS). Angioplasty was performed via right carotido tomy on both iliac arteries using an oversized balloon catheter, the TTA gr oup being pretreated for 3 weeks. After angioplasty, the lumen diameter was 2.37 +/- 0.18 versus 2.36 +/- 0.13 mm for the TTA and control groups, resp ectively (P = NS). At 10 weeks follow-up angiography, minimal luminal diame ter was 1.64 +/- 0.27 versus 1.13 +/- 0.52 mm for the TTA and control group s respectively (P < 0.05). Histomorphometry did not show significant differ ences in intimal hyperplasia between the two groups (maximal intimal thickn ess 0.22 +/- 0.04 versus 0.19 +/- 0.10 mm, P = NS and intimal area 0.32 +/- 0.12 versus 0.36 +/- 0.23 mm(2), P = NS for the TTA and the control groups , respectively). In the heart, the sum of the n-3 fatty acids was 8.9 +/- 2 .7 in the TTA group versus 4.3 +/- 0.2 mol% in the control group (P < 0.05) . The anti-inflammatory fatty acid index, calculated as (22:5 n-3 + 22:6 n- 3 + 20:3 n-6)/20:4 n-6, was 0.76 +/- 0.10 vs. 0.25 +/- 0.03 for the TTA and control groups, respectively (P < 0.05). In vitro TTA (100 <mu>M) reduced the proliferation of human smooth muscle cell by more than 50%. Conclusion: treatment with TTA is associated with positive arterial remodeling after a ngioplasty injury. The significance of the in vitro inhibition of human smo oth muscle cell proliferation needs to be further elucidated. (C) 2001 Else vier Science Ireland Ltd. All rights reserved.