Down-regulation of autophagy-related gene 5 inhibits venous bridge stenosis

Abstract

Objective To determinate the role of autophagy-related gene 5 (Atg5) in the stenosis of vein graft after inferior vena cava transplantation in mice. Methods Thirty male C57BL/6 wild type mice and 20 Atg5+ /- mice were divided randomly into into a WT sham operation group (n=10), a WT surgery group (10 recipients, 10 donors), and an Atg5+ /- surgery group (10 recipients, 10 donors). HE staining was used to detect the stenosis of vein graft. The mRNA level of Atg5 and LC3 was detect by Real-time PCR. The protein of Atg5 and LC3 were measured by Westem-Blot. Immunofluorescence was used to analyze the specific cell type. Results The lumen of vein grafts in Atg5+ /- mice at 4 weeks after the inferior vena cava transplantation was wider than that in WT mice [(4.21±0.32)×104 μm2vs. (1.63±0.15) ×104 μm2, P<0.05], with increased Atg5 [(0.51±0.17)×10-3vs. (1.49±0.08)×10-3], LC3[(1.9±0.4)×10-2vs. (3.8±0.9)×10-2] mRNA expression in vein graft of WT mice (all P < 0.05). Compared with the WT mice, there were significant less Atg5 [(0.39±0.05) vs. (0.16±0.08)], LC3[(2.17±0.46) vs. (0.78±0.19)] in vein graft of Atg5+ /- mice (all P < 0.05). Similarly, the expression of LC3 in smooth muscle cells of Atg5+ /- vein graft was significantly decreased (P<0.05), and the lumen of vein graft in Atg5+ /- mice was significantly decreased than that in WT mice [(1.63±0.15) ×104 μm2vs.(2.96±0.12)×104 μm2,P<0.05]. Conclusions Our results demonstrate that Atg5 deficiency inhibited the stenosis of vein graft. Key words: Vein graft; Smooth muscle cells; Authopagy; Atg5