P 120 - Dietary Sulforaphane supplementation induces Nrf2, attenuating hypoxia-induced vascular smooth muscle cell proliferation and remodelling following carotid artery ligation: Abstracts of the OCC World Congress and Annual SFRR-E Conference 2017 Metabolic Stress and Redox Regulation Berlin, Germany 21-23 June 2017

TY - JOUR

T1 - P 120 - Dietary Sulforaphane supplementation induces Nrf2, attenuating hypoxia-induced vascular smooth muscle cell proliferation and remodelling following carotid artery ligation

T2 - Abstracts of the OCC World Congress and Annual SFRR-E Conference 2017 Metabolic Stress and Redox Regulation Berlin, Germany 21-23 June 2017

AU - Chapple, Sarah

AU - Burford, Charlotte

AU - Farrell-Dillon, Keith

AU - Mann, Giovanni

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - Vascular

KW - Nrf2

KW - smooth muscle

KW - sulforaphane

U2 - 10.1016/j.freeradbiomed.2017.04.205

DO - 10.1016/j.freeradbiomed.2017.04.205

M3 - Meeting abstract

SN - 0891-5849

VL - 108, Supplement 1

SP - S59

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -