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Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:470-476
Published online before print January 15, 2004, doi: 10.1161/01.ATV.0000116865.98067.31
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:470.)
© 2004 American Heart Association, Inc.


Vascular Biology

Graft-Extrinsic Cells Predominate in Vein Graft Arterialization

Lisheng Zhang; Neil J. Freedman; Leigh Brian; Karsten Peppel

From the Duke University Department of Medicine (Cardiology), Duke University Medical Center, Durham, NC.

Correspondence to Karsten Peppel, Box 3187, Duke University Medical Center, 447 CARL Building, Science Drive, Durham, NC 27710. E-mail karsten.peppel{at}duke.edu

Objective— Vein graft disease involves neointimal smooth muscle cells, the origins of which are unclear. This study sought to characterize and quantitate vein graft infiltration by cells extrinsic to the graft in a mouse model of vein graft disease.

Methods and Results— Inferior vena cava-to-carotid artery interposition grafting between C57Bl/6 and congenic ß-galactosidase–expressing ROSA26 mice was performed. Vein grafts were harvested 6 weeks postoperatively and stained with X-gal. More than 60% of neointimal cells derived from the recipient, and 50% of these cells expressed smooth muscle {alpha}-actin. The distribution of donor and recipient-derived cells within this vein graft wall layer was distinctly focal, consistent with focal infiltration and expansion of progenitor cells. When bone marrow transplantation with congenic green fluorescent protein (GFP)-expressing cells was used in vein graft recipients 1 month before surgery, abundant GFP-expressing cells appeared in the media, but not the neointima, of mature grafts. Endothelial cells in mature grafts derived from graft-intrinsic and graft-extrinsic sources and were, in part, of bone marrow origin.

Conclusions— Cells extrinsic to the graft, including bone marrow-derived cells, predominate during vein graft remodeling.


Key Words: smooth muscle cells • vein graft neointimal hyperplasia • mouse models • bone marrow transplantation • endothelium




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