Effect of arsenic trioxide on inhibition of restenosis after rabbit vascular injury and its mechanism.
OBJECTIVE
To investigate the effect and mechanism of arsenic trioxide (As(2)O(3)) on the prevention of restenosis after vascular injury.


METHODS
Apoptosis induction of As(2)O(3) on cultured rabbit vascular smooth muscle cells (VSMCs) in vitro was observed. Thirty-two New Zealand white rabbits were randomly divided into 2- and 4-wk study groups, and their controls. 10% As(2)O(3) at 2.5 mg x Kg(-1) x d(-1) or 0.9% sodium chloride was intraperitoneally infused for 3 days before left common carotid arteries were denudated with a balloon. After denudation 2- and 4-wk animals were sacrificed for morphometry and immunohistochemical studies on carotid arteries, and for histopathology on liver and kidney.


RESULTS
It was shown via cellular morphology and DNA fragments in electrophoresis that promotion of As(2)O(3) on cultured vascular smooth muscle cell apoptosis was dependent upon its concentration and duration. Compared with the control animals, the mean vascular intimal proliferation areas were reduced in 2-wk study animals (P < 0.05) and no difference was shown in 4-wk (P > 0.05), while the mean vascular luminal areas were all enlarged in both study groups (all P < 0.05). The downregulated bcl-2 expression (all P < 0.05 in 2- and 4-wk) and the upregulated bax expression (P < 0.01 in 2-wk; P < 0.05 in 4-wk) were detected by immunohistochemistry, in comparison with control groups. Gene bcl-2 and bax protein expression were consistent with the suppression of intimal proliferation and the enlargement of luminal areas in corresponding sections.


CONCLUSIONS
As(2)O(3) induces apoptosis of VSMCs and inhibits experimental restenosis effectively after artery injury, via downregulation of bcl-2 and upregulation of bax expression.
Zhao
Zhishen
Z
Division of Cardiology, Renmin Hospital, Wuhan University Medicine School, Wuhan 430060, China.
Huang
Congxin
C
Wang
Jing
J
Jiang
Hong
H
Li
Jianjun
J
Wang
Xi
X
D000818:Animals; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D004247:DNA / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011817:Rabbits; D014652:Vascular Diseases / Q000517:prevention & control*; D051028:bcl-2-Associated X Protein
D001152:Arsenicals; D010087:Oxides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004247:DNA; D000077237:Arsenic Trioxide