Mechanisms underlying the inhibitory effects of probucol on elastase-induced abdominal aortic aneurysm in mice

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 has been widely applied to treat hyperlipidaemia and atherosclerosis in clinic, but whether it can protect against AAA remains unknown. In this study, the protective effects of probucol against AAA and its related mechanisms were explored. Experimental approach: The model of AAA was induced in mice by periaortic application of elastase (40 min) to the abdominal aorta. Probucol at different doses was administered by daily gavage, starting on the same day as AAA was induced, for 14 days. In vitro, cultures of rat vascular smooth muscle cells (VSMCs) were stimulated with TNF-α. Haem 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

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 has been widely applied to treat hyperlipidaemia and atherosclerosis in clinic, but whether it can protect against AAA remains unknown. In this study, the protective effects of probucol against AAA and its related mechanisms were explored. Experimental approach: The model of AAA was induced in mice by periaortic application of elastase (40 min) to the abdominal aorta. Probucol at different doses was administered by daily gavage, starting on the same day as AAA was induced, for 14 days. In vitro, cultures of rat vascular smooth muscle cells (VSMCs) were stimulated with TNF-α. Haem 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

Probucol dose-dependently prevented the development of AAA, reflected by decreased incidence of AAA, diameter of aortic dilation, elastin degradation, and infiltration of inflammatory cells. Probucol also protected VSMCs from oxidative injury and enhanced elastin biosynthesis. This anti-inflammatory effects of probucol on VSMCs were significantly decreased when HO-1 was inhibited by siRNA.