REMODELING OF AUTOLOGOUS SAPHENOUS-VEIN GRAFTS - THE ROLE OF PERIVASCULAR MYOFIBROBLASTS

Background Aortocoronary saphenous vein grafts (SVGs) undergo structur al changes that render them susceptible to atherosclerosis. Accordingl y, the origin of neointimal hyperplasia was examined in porcine arteri alized SVGs to determine the mechanism of vein graft remodeling. Metho ds and Results At 2 to 4 days after surgery, the percentage of cells l acking differentiation markers characteristic for smooth muscle (SM) c ells (ie, a alpha-SM actin, desmin, and SM myosin) increased within th e media of SVGs interposed in the carotid arteries (P < .001). At 7 to 14 days, these cells acquired a differentiated phenotype (ie, alpha-S M-actin positive/variable desmin/SM-myosin negative) and accumulated i n the neointima. At 3 months, the neointima was positive for alpha-SM actin but mostly negative for desmin, which contrasted with medial SMC s that were invariably positive for alpha-SM actin, desmin, and SM myo sin. To determine the role of nonmuscle cells in the above process, pe rivascular wound fibroblasts were selectively labeled and found to tra nslocate through the media of newly placed SVGs, contributing to neoin timal formation. These migrating cells differentiated to myofibroblast s exhibiting sustained alpha-SM-actin expression. The intima of human SVGs, retrieved during repeat aortocoronary bypass surgery, exhibited the profile of cytoskeletal proteins that resembled myofibroblasts see n in porcine SVGs. Conclusions Perivascular fibroblasts may infiltrate injured media of arterialized SVGs, differentiate to myofibroblasts ( acquiring alpha-SM actin), and contribute to vein graft remodeling. Th e similarities between porcine and human SVGs regarding the repertoire of cytoskeletal proteins suggest the involvement of myofibroblasts in graft remodeling in the clinical setting.