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Butylated hydroxyanisole stimulates heme oxygenase‐1 gene expression and inhibits neointima formation in rat arteries
Author(s) -
Durante William,
Liu Xiaoming,
Azam Mohammed A.,
Ensenat Diana,
Keswani Amit N.,
Wang Hong,
Peyton Kelly J.
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1129
Butylated hydroxyanisole (BHA) is a synthetic phenolic compound that is a potent inducer of phase II genes. Since heme oxygenase‐1 (HO‐1) is a vasoprotective protein that is upregulated by phase II inducers, the present study examined the effects of BHA on HO‐1 gene expression and vascular smooth muscle cell (SMC) proliferation. Treatment of cultured rat aortic SMC with BHA (10–300μM) stimulated the expression of HO‐1 protein, mRNA and promoter activity in a time‐ and concentration‐dependent manner. The induction of HO‐1 expression by BHA was dependent on the activation of the Nrf2/Antioxidant responsive element complex. In addition, BHA inhibited serum‐stimulated cell cycle progression and DNA synthesis in vascular SMC, and this was prevented by the HO inhibitor, tin protoporphyrin‐IX (10μM). Furthermore, the local perivascular delivery of BHA immediately after balloon injury of rat carotid arteries induced HO‐1 protein expression and markedly attenuated neointima formation. These studies demonstrate that BHA stimulates HO‐1 gene expression in vascular SMC, and that the induction of HO‐1 contributes to the antiproliferative actions of this phenolic antioxidant. BHA represents a potentially novel therapeutic agent in treating or preventing vasculoproliferative disease. Supported by NIH R01 HL59976.