Abstract 3444: The Effect of Alpha Lipoic Acid on Porcine Coronary Stent Restenosis

Abstract

Objective: We evaluated the ability of alpha lipoic acid (ALA) to affect on coronary instent restenosis (ISR) in a porcine model. Methods: In vitro experiment: We stimulated porcine VSMC using G-CSF in the presence or absence of ALA. Activation of Akt, vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription (STAT)-3 were determined using western blot. And also, cell proliferation and migration assay were determined. In vivo experiment:Balloon overdilation injuries were performed in 2 coronary arteries in 12 pigs. Four weeks after the balloon overdilation injury, 24 bare metal stents were placed for 24 injured coronary arteries. We randomized into two groups (12 stents per group; control group: aspirin and clopidogrel only, ALA group: aspirin and clopidogrel plus 100 mg/kg ALA during 4 weeks). 16 bare metal stents were implanted randomized two coronary arteries in 8 pigs. Group I was control stent group (n=8), Group II was ALA coated stent group (n=8). Follow-up coronary angiogram (CAG) and histopathologic assessment were performed at 4 weeks after stenting. Results: G-CSF increased the phosphorylation of ERK and STAT-3, but after pretreatment of ALA, the phosphorylation of ERK and STAT-3 were significantly reduced. On histopathologic analysis, injury score, internal elastic lamina(IEL) area did not differ significantly between the two groups. The neointimal area was 7.3±0.9 mm2 in control group and 2.2±1.1 mm2 in ALA group (p<0.001), and the histopathologic area of stenosis(AS) was 75.9±8.5 % in control group, 23.5±10.5 % in ALA group (p<0.001). The injury score and IEL area were not significantly different between the two groups. The neointimal area was 7.4±1.1 mm2 in control group and 1.4±0.8 mm2 in ALA group (p<0.001), and the AS was 77.6±10.9 % in control group, 15.6±7.6 % in ALA group (p<0.001). The number of inflammatory cells within neointima was lower in ALA group (63.2±23.7 % vs. 17.6±11.6 %, p<0.001). Conclusion: ALA inhibits the activation of ERK, STAT-3 and proliferation of VSMC. Both high dose of oral ALA and ALA coated stents inhibit neointimal hyperplasia in a porcine ISR model