LAUSR

BACKGROUND AND PURPOSE Abdominal aortic aneurysm (AAA) is a degenerative disease with irreversible and progressive dilation of the artery. But there are few options for efficacious treatment except for traditional surgery. Probucol (PB) has been widely applied to treat hyperlipidemia and atherosclerosis in clinic, but whether it can protect against AAA remains unknown. In this study, the protective effects of PB against AAA and its related mechanisms were explored. EXPERIMENTAL APPROACH Mouse AAA model was induced by incubating the abdominal aorta with elastase. PB at different doses was administrated to the mice by gavage beginning on the same day of AAA inducement and lasted for 14 days. In vitro experiments were constructed by stimulating rat vascular smooth muscle cells (VSMCs) with tumor necrosis factor (TNF)-α. Heme oxygenase (HO)-1 siRNA and HO-1 plasmid were used to regulate the expression or activity of HO-1 in the VSMCs and to clarify the effects of HO-1. KEY RESULTS PB dose-dependently prevented the development of AAA, reflected by decrease of AAA incidence, diameters of aortic dilation, elastin degradation and inflammatory cells infiltration. PB could also protect VSMCs from oxidative injury and enhance elastin biosynthesis. But the anti-inflammatory effect of PB on VSMCs was weakened significantly when HO-1 was inhibited by siRNA. CONCLUSION AND IMPLICATIONS PB exerted anti-AAA effects through inhibiting the degradation of elastin caused by inflammation and oxidation and facilitating the biosynthesis of elastin. HO-1 plays a crucial role in anti-inflammatory effect of PB on VSMCs.