Sulforaphane inhibits restenosis by suppressing inflammation and the proliferation of vascular smooth muscle cells.
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.
Heart Research Center of Chonnam National University Hospital, Jebong-ro, Dong-ku, Gwangju 501-757, Republic of Korea.
Jin-Sook
JS
Kwon
Hosouk
H
Joung
Yong Sook
YS
Kim
Young-Sun
YS
Shim
Youngkeun
Y
Ahn
Myung Ho
MH
Jeong
Hae Jin
HJ
Kee
D000818:Animals; D050993:GATA6 Transcription Factor / Q000096:biosynthesis / Q000378:metabolism; D020672:I-kappa B Proteins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D017879:Isothiocyanates; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D032389:Myocytes, Smooth Muscle; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D058426:Neointima / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D050993:GATA6 Transcription Factor; C084364:Gata6 protein, rat; D020672:I-kappa B Proteins; D017879:Isothiocyanates; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D013454:Sulfoxides; D013861:Thiocyanates; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C016766:sulforaphane