The effect of alpha lipoic acid in a porcine in-stent restenosis model

Sang Yeob Lim, Eun Hui Bae, Myung Ho Jeong, Ju Han Kim, Young Joon Hong, Doo Sun Sim, Yong Sook Kim, In Kyu Park, Youngkeun Ahn, Sun Jung Song, Dong Lyun Cho, Kyoung Seok Kim, Jung Chaee Kang

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Abstract

Background: The aim of this study was to investigate the effect of alpha lipoic acid (α-LA) on a porcine in-stent restenosis (ISR) model. Methods: In protocol 1, porcine vascular smooth muscle cells (PVSMC) were stimulated by granulocyte-colony stimulating factor (G-CSF) in the presence or absence of α-LA. MTT (3-[4,5-dimethylthiazole-2-yl] 2,5-diphenyl tetrazolium bromide) assay and western blotting were used to determine the cell growth inhibitory rate and anti-inflammatory effect associated with nuclear factor-κb (NF-κb) and extracellular signal-regulated kinase (ERK). In protocol 2, 28 days after balloon overdilation injuries, 24 bare metal stents were placed in coronary artery of 12 pigs. The pigs were randomly divided to receive control diet with or without α-LA (100 mg/kg). In protocol 3, 8 control stents and 8 α-LA coated stents were randomly implanted in 2 coronary arteries of 8 pigs and follow-up coronary angiogram and histopathologic assessment were performed 4 weeks after stenting. Results: Protocol 1. The proliferation of PVSMC was inhibited and protein expression of NF-κb and ERK were attenuated by α-LA pretreatment. Protocol 2. On histopathologic analysis, the neointimal area (4.0 ± 1.0 mm2 vs. 1.5 ± 0.7 mm2, p < 0.001) and histopathologic area of stenosis (66.7 ± 10.7% vs. 24.2 ± 9.7%, p < 0.001) were reduced in the α-LA feeding group compared to controls. Protocol 3. On histopathologic analysis, the neointimal area (3.9 ± 0.8 mm2 vs. 1.0 ± 0.4 mm2, p < 0.001), and the histopathologic area of stenosis (67.1 ± 8.8% vs. 17.4 ± 10.0%, p < 0.001) were reduced in the α-LA coated stent group compared to the control stent group. Conclusions: α-LA feeding and α-LA coated stents inhibit neointimal hyperplasia in porcine ISR, possibly through inhibiting the activation of NF-κb pathway and proliferation of PVSMC.

Original languageEnglish
Pages (from-to)375-385
Number of pages11
JournalJournal of Cardiology
Volume54
Issue number3
DOIs
Publication statusPublished - 2009 Dec 1

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Keywords

  • Endothelium
  • Inflammation
  • Restenosis
  • Stents

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lim, S. Y., Bae, E. H., Jeong, M. H., Kim, J. H., Hong, Y. J., Sim, D. S., Kim, Y. S., Park, I. K., Ahn, Y., Song, S. J., Cho, D. L., Kim, K. S., & Kang, J. C. (2009). The effect of alpha lipoic acid in a porcine in-stent restenosis model. Journal of Cardiology, 54(3), 375-385. https://doi.org/10.1016/j.jjcc.2009.06.005