Upregulation of miR-423 improves autologous vein graft restenosis via targeting ADAMTS-7

Coronary artery bypass graft (CABG) is one of the primary methods of treating coronary heart disease (CHD); however, vein graft restenosis is a major limiting factor of the effectiveness of CABG. Emerging evidence has indicated that miR-423 is associated with vascular diseases. Additionally, upregulation of a disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7) contributes to neointima formation by promoting the proliferation and migration of vascular smooth muscle cells and inhibiting the proliferation and migration of endothelial cells. The aim of the present study was to examine the effects of miR-423 target, ADAMTS-7, on regulating vein graft disease and identify novel biomarkers for use in therapy of vein graft failure (VGF). Aberrant expression of miR-423 in plasma of patients with CHD prior to and following CABG confirms that miR-423 may be a suitable target for preventing VGF. Furthermore, a dual-luciferase reporter gene assay indicated that miR-423 directly interacted with ADAMTS-7 and suppressed its expression. Ectopic expression of miR-423 suppressed ADAMTS-7, resulting in decreased proliferation and migration rates of human umbilical vein smooth muscle cells by targeting ADAMTS-7, but resulted in increased proliferation and migration of human umbilical vein endothelial cells in vitro. Overexpression of miR-423 also enhanced re-endothelialization and decreased neointimal formation in a rat vein graft model. In conclusion, the results of the present study demonstrated that the miR-423/ADAMTS-7 axis may possess potential clinical value for the prevention and treatment of restenosis in patients with CHD following CABG.