Dietary Sulforaphane supplementation induces Nrf2, attenuating hypoxia-induced vascular smooth muscle cell proliferation and remodelling following carotid artery ligation

We sought to assess whether dietary sulforaphane (SFN) supplementation to C57BL/6 J mice attenuates injury following carotid artery ligation, in which the endothelium remains intact. We also sought to establish whether SFN-induced induction of Nrf2 redox defence genes underlies hypoxia-induced proliferation of vascular smooth muscle cells and may therefore contribute towards vascular injury protection. Pre-treatment with a physiologically achievable (0.5 mg/kg) dose of SFN and continued administration 2 and 4 weeks post ligation was associated with Nrf2-dependent gene expression (e.g. heme oxygenase 1, HO-1) and reduced neointimal formation assessed by Van Gieson staining. Using an oxygen regulated work station, exposure of primary mouse aortic smooth muscle cells (MASMC, P2) to hypoxia (1% O2) enhanced proliferation when assessed by cell count and protein expression. In SFN (2.5 µM) treated MASMC, proliferation was attenuated following serum challenge (10% FCS) for 72 h and correlated with Nrf2 target gene induction. Overall our results suggest that independent of endothelial oxidative damage, reduced oxygen availability enhances vascular smooth muscle cell proliferation. SFN supplementation induces Nrf2 defences and reduces smooth muscle cell proliferation, suggesting dietary Nrf2 supplementation may provide a useful therapeutic intervention to promote vascular health.