Murine model of neointimal formation and stenosis in vein grafts.
OBJECTIVE
Previous studies have suggested that neointimal formation, a central cause of vein graft stenosis, has several potential cell sources. It was hypothesized that neointimal cells arise primarily from the cells of the vein graft.


RESULTS
This study investigated vein graft neointimal cell origins using a model of vein-to-artery cross-transplantation between transgenic Rosa26 mice (constitutive expression of bacterial beta-galactosidase marker gene) and wild-type mice. Vein-originating cells survived and make a major contribution to neointimal formation within the vein graft, mostly adjacent to the lumen/endothelium, suggesting an intimate association with endothelial cells. Cross-transplantation of veins from thrombomodulin promoter-driven beta-galactosidase reporter transgenic mice to wild-type arteries demonstrated survival of vein graft endothelial cells. Neointimal thickening was greater at the proximal and, to a lesser extent, distal ends, in comparison to the middle of the graft. By contrast, arterial grafts had almost no neointimal formation throughout the graft. The relative neointimal wall thickness is much greater in this model compared with other murine and larger-species vein graft models, even showing near-occlusive stenosis of the perianastomotic region.


CONCLUSIONS
Vein graft neointimal cells arise predominantly from vein-derived cells, suggesting clinical relevance of stenosis-inhibiting therapies directed at the vein graft.
Cooley
Brian C
BC
Allen Bradley Medical Sciences Laboratory, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. bcooley@mcw.edu
D000818:Animals; D001807:Blood Vessel Prosthesis; D019070:Cell Lineage; D002470:Cell Survival; D004730:Endothelium, Vascular / Q000473:pathology; D005263:Femoral Artery / Q000601:surgery*; D017930:Genes, Reporter; D006083:Graft Occlusion, Vascular; D006085:Graft Survival; D006965:Hyperplasia; D007601:Jugular Veins / Q000166:cytology / Q000637:transplantation*; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D018180:Thrombomodulin / Q000235:genetics; D017539:Tunica Intima / Q000473:pathology*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D011993:Recombinant Fusion Proteins; D018180:Thrombomodulin; D001616:beta-Galactosidase