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 lipoprotein particles in vitro. We examined the influence of TTA on the arterial wall response after balloon angioplasty injury in a rabbit iliac model. Methods and results: 14 rabbits were randomized to receiving either TTA fatty acids 800 mg daily perorally (weight 3.6±0.1 kg) or to normal diet (weight 3.5±0.5 kg, P=NS). Angioplasty was performed via right carotidotomy on both iliac arteries using an oversized balloon catheter, the TTA group 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, respectively (P=NS). At 10 weeks follow-up angiography, minimal luminal diameter was 1.64±0.27 versus 1.13±0.52 mm for the TTA and control groups respectively (P<0.05). Histomorphometry did not show significant differences in intimal hyperplasia between the two groups (maximal intimal thickness 0.22±0.04 versus 0.19±0.10 mm, P=NS and intimal area 0.32±0.12 versus 0.36±0.23 mm2, 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 μM) reduced the proliferation of human smooth muscle cell by more than 50%. Conclusion: treatment with TTA is associated with positive arterial remodeling after angioplasty injury. The significance of the in vitro inhibition of human smooth muscle cell proliferation needs to be further elucidated.