Abstract
Neointima formation is the major reason for vein graft failure. However, the underlying mechanism is unclear. The aim of this study was to determine the role of miR-26a in the development of neointimal hyperplasia of autogenous vein grafts. Using autologous jugular vein grafts in the rat carotid artery as a model, we found that miR-26a was significantly downregulated in grafted veins as well as proliferating vascular smooth muscle cells (VSMCs) stimulated with platelet-derived growth factor-BB (PDGF-BB). Overexpression of miR-26a reduced the proliferation and migration of VSMCs. Further analysis revealed that the effects of miR-26a in VSMCs were mediated by targeting MAPK6 at the mRNA and protein levels. Luciferase assays showed that miR-26a repressed wild type (WT) MAPK6-3'-UTR-luciferase activity but not mutant MAPK6-3'-UTR-luciferease reporter. MAPK6 deficiency reduced proliferation and migration; in contrast, overexpression of MAPK6 enhanced the proliferation and migration of VSMCs. This study confirmed that neointimal hyperplasia in vein grafts was reduced in vivo by up-regulated miR-26a expression. In conclusion, our results showed that miR-26a is an important regulator of VSMC functions and neointimal hyperplasia, suggesting that miR-26a may be a potential therapeutic target for autologous vein graft diseases.