Salvianolic Acid B Inhibits Atherogenesis of Vascular Cells through Induction of Nrf2-dependent Heme Oxygenase-1
Hyun Jung Lee,
Eun Jig Lee.
Aims: Salvianolic acid B (Sal B), one of the most active components of Danshen extracts, has beneficial roles
in the prevention and treatment of cardiovascular diseases. However, the precise mechanism by which Sal B exerts its effects
on vascular cells is unclear. We aimed to elucidate the effects of Sal B on vascular cells and the underlying mechanisms.
Methods and Results: Treatment of vascular smooth muscle cells with Sal B effectively inhibited platelet-derived
growth factor (PDGF)-induced cell proliferation and migration, and markedly increased heme oxygenase-1 (HO-1) expression.
These changes were accompanied by antioxidant effects, including decreases in the generation of reactive oxygen
species and the NADP/NADPH ratio. In human umbilical vein endothelial cells, Sal B also strongly induced HO-1
and effectively inhibited tumor necrosis factor-α-induced NF-κB activation. Knockdown of HO-1 expression by siRNA
abolished the effects of Sal B in vascular cells and prevented the inhibition of proliferation, migration, and inflammation
in HO-1-deficient cells. In ex vivo culture of arterial rings isolated from nuclear factor-E2-related factor 2 (Nrf2)-knockout
mice, Sal B neither induce HO-1 expression and nor inhibit PDGF-induced neointimal hyperplasia in arteries, suggesting
that Nrf2 plays a crucial role in the induction of HO-1 expression. Conclusions: We conclude that Sal B exerts antiatherogenic
effects by inhibiting the proliferation, migration, and inflammation of vascular cells through induction of HO-1 via
Keywords: HO-1, HUVEC, inflammation, Nrf2, proliferation, Salvianolic acid B, VSMC.
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