title: Effect of alpha lipoic acid in a porcine in-stent restenosis model.
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 mm(2) vs. 1.5+/-0.7 mm(2), 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 mm(2) vs. 1.0+/-0.4 mm(2), 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.
authors: The Cardiovascular Center of Korea University Ansan Hospital, Seoul, Republic of Korea.
authors: Sang Yup
authors: SY
authors: Lim
authors: Eun Hui
authors: EH
authors: Bae
authors: Myung Ho
authors: MH
authors: Jeong
authors: Ju Han
authors: JH
authors: Kim
authors: Young Joon
authors: YJ
authors: Hong
authors: Doo Sun
authors: DS
authors: Sim
authors: Yong Sook
authors: YS
authors: Kim
authors: In Kyu
authors: IK
authors: Park
authors: Youngkeun
authors: Y
authors: Ahn
authors: Sun-Jung
authors: SJ
authors: Song
authors: Dong Lyun
authors: DL
authors: Cho
authors: Kyoung Seok
authors: KS
authors: Kim
authors: Jung Chaee
authors: JC
authors: Kang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D005260:Female; D006965:Hyperplasia; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D058426:Neointima / Q000473:pathology; D015607:Stents / Q000009:adverse effects*; D013552:Swine; D008063:Thioctic Acid / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D008063:Thioctic Acid