Abstract
Vascular remodelling triggering the proliferation, differentiation and migration of vascular smooth muscle cells (VSMCs) into the vessel lumen occurs during atherosclerosis or restenosis and results in a narrowing of the blood vessel lumen, leading to a reduction in blood flow. The dietary isothiocyanate Sulforaphane (SFN) attenuates vascular remodelling, however its mechanism of action is poorly defined. This study sought to determine whether p62 induction underlies SFN mediated protection. Wildtype C57BL/6 8-week-old mice were supplemented with SFN (0.5 mg/kg) daily for 2 weeks before carotid artery ligation. Ligation induced a time-dependent thickening of the medial layer, with pronounced neointimal formation observed 4 weeks post ligation. SFN stabilised medial thickening (78307 vs 74103) and significantly attenuated neointimal formation (116664 vs 41465µm2) and stenosis (1.5 vs 0.6 stenotic ratio). In contrast SFN failed to attenuate either medial thickening or neointimal formation in p62-/- mice. Moreover, in isolated murine aortic VSMCs, SFN (2.5 µM) induced p62 expression and inhibited VSMC proliferation. Our study suggests p62 induction by SFN may underlie SFN mediated protection against vascular remodelling and may provide a novel target for therapeutic intervention.
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