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Sulforaphane inhibits restenosis by suppressing inflammation and the proliferation of vascular smooth muscle cells.

Abstract：

OBJECTIVE:Sulforaphane, a naturally occurring organosulfur compound in broccoli, has chemopreventive properties in cancer. However, the effects of sulforaphane in vascular diseases have not been examined. We therefore aimed to investigate the effects of sulforaphane on vascular smooth muscle cell (VSMC) proliferation and neointimal formation and the related mechanisms. METHODS:The expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) was examined in VSMCs. The nuclear translocation of nuclear factor-κB (NF-κB) and GATA6 expression was examined in VSMCs and in a carotid artery injury model by Western blot and immunohistochemistry. We also investigated whether local delivery of sulforaphane affected neointimal formation. RESULTS:Sulforaphane inhibited the mRNA and protein expression of VCAM-1 induced by tumor necrosis factor (TNF)-α in VSMCs. Treatment of VSMCs with sulforaphane blocked TNF-α-induced IκBα degradation and NF-κB p65 and GATA6 expression. Furthermore, NF-κB p65 and GATA6 expression were reduced in sulforaphane-treated carotid injury sections. Notably, binding of GATA6 to the VCAM-1 promoter was dramatically reduced by sulforaphane. The MTT, BrdU incorporation, and in vitro scratch assays revealed that the proliferation and migration of VSMCs were reduced by sulforaphane. Furthermore, local administration of sulforaphane significantly reduced neointima formation 14 days after vascular injury in rats. CONCLUSIONS:Our results indicate that sulforaphane inhibits neointima formation via targeting of adhesion molecules through the suppression of NF-κB/GATA6. Furthermore, sulforaphane regulates migration and proliferation in VSMCs. Sulforaphane may be a potential therapeutic agent for preventing restenosis after vascular injury.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Kwon JS,Joung H,Kim YS,Shim YS,Ahn Y,Jeong MH,Kee HJ

doi

10.1016/j.atherosclerosis.2012.07.040

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

41-9

issue

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(12)00516-3

journal_volume

225

pub_type

杂志文章

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Sulforaphane inhibits restenosis by suppressing inflammation and the proliferation of vascular smooth muscle cells.