Effect of alpha lipoic acid in a porcine in-stent restenosis model.
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.
Lim
Sang Yup
SY
The Cardiovascular Center of Korea University Ansan Hospital, Seoul, Republic of Korea.
Bae
Eun Hui
EH
Jeong
Myung Ho
MH
Kim
Ju Han
JH
Hong
Young Joon
YJ
Sim
Doo Sun
DS
Kim
Yong Sook
YS
Park
In Kyu
IK
Ahn
Youngkeun
Y
Song
Sun-Jung
SJ
Cho
Dong Lyun
DL
Kim
Kyoung Seok
KS
Kang
Jung Chaee
JC
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*
D008063:Thioctic Acid