Abstract 16135: The Role of Circulating versus Local Progenitor Cells in Vein Stenosis
Background: Neointimal hyperplasia is a major clinical problem that compromises the long-term patency of coronary bypass grafts and causes the failure of arteriovenous (AV) fistulas in hemodialysis patients. This study aims to elucidate the anatomical source(s) of vein neointimal cells in an experimental model of AV fistula failure.
Methods and Results: To assess the role of bone marrow (BM) derived cells in the remodeling of the fistula wall, chimeras were created by rescuing lethally irradiated wild type (WT) Lewis rats with GFP+ BM cells from transgenic animals. 95.40 ± 8.21% of blood peripheral cells in chimeras were GFP+ at the time of fistula creation. The aorto-caval fistula was created by anastomosing the left renal vein to the abdominal aorta after unilateral nephrectomy. Three weeks post surgery, animals were sacrificed and frozen sections from fistulas were immunostained with antibodies specific for vascular smooth muscle cell markers. Single GFP stained cells were imaged in depth Z-series acquired by confocal scanning laser microscopy. GFP cells were abundant in the fistula wall yet only few were GFP+ Smooth Muscle Actin (SMA)+ within the neointima (0.21% ± 0.02, n=6)demonstrating that neointimal cells in venous limb of the fistula do not originate from bone marrow. Next, we created a fistula using a GFP aortic graft previously transplanted to a WT recipient to assess the contribution of arterial versus recipient cells to the neointimal formation. Again, most of neointima cells (>99.9%, n=4) turned GFP- SMA+ showing no contribution of cells from the feeding artery to vein stenosis. Finally to prove that neointimal cells in AV fistulas were originated from pre-existing cells in the vein, we interposed vein grafts from GFP transgenic rats between the renal vein and the aorta of the WT recipients at the time of fistula creation. Neointimal cells in the graft were GFP+ SMA+ (98.9%, n=5) and in the recipient vein were mostly GFP- SMA+ (99.3%, n=5).
Conclusion: The results of this study demonstrate that neointimal cells in the rat AVF model are mostly derived from pre-existing cells in the vein and not from the circulating progenitors.
- © 2010 by American Heart Association, Inc.