Published online before print December 1, 2003, doi: 10.1161/01.CIR.0000105722.96112.67
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(Circulation. 2003;108:3122-3127.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Endothelial Replacement and Angiogenesis in Arteriosclerotic Lesions of Allografts Are Contributed by Circulating Progenitor Cells
From the Department of Cardiological Sciences, St George’s Hospital Medical School, London, United Kingdom.
Correspondence to Prof Qingbo Xu, Department of Cardiological Sciences, St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. E-mail q.xu{at}sghms.ac.uk
Received March 26, 2003; de novo received June 27, 2003; revision received August 18, 2003; accepted August 19, 2003.
Background— Endothelial regeneration and angiogenesis in the intima of the arterial wall are key events in the pathogenesis of transplantation arteriosclerosis. The traditional hypothesis that damaged endothelial cells are replaced by remaining cells of the donor vessel has been challenged by recent observations, but the cell origins of large arteries and microvessels are still not well established.
Methods and Results— Aortic segments were allografted between Balb/c and TIE2-LacZ (C57BL/6) mice expressing ß-galactosidase (gal) in endothelial cells. ß-gal+ cells in TIE2-LacZ vessels grafted to Balb/c mice completely disappeared, whereas the positive cells found in Balb/c aorta allografted into TIE2-LacZ mice 4 weeks after surgery indicated a host origin. En face analysis of allograft vessels displayed a unique distribution of ß-gal+ cells on the surface at 3 days, 1 week, and 4 weeks. Interestingly, 35±19% ß-gal+ cells were found in arterial segments allografted into chimeric mice with TIE2-LacZ bone marrows. Furthermore, endothelial cells of microvessels within allografts had a ß-gal+ staining in the media at 1 week and in the neointimal lesions and adventitia at 4 weeks. Allograft studies in chimeric mice demonstrated that ß-gal+ cells of microvessels in transplant arteriosclerosis were derived from bone marrow progenitors.
Conclusions— We provide strong evidence that endothelial cells of neointimal lesions in allografts are derived from circulating progenitor cells and that bone marrow–derived progenitors are responsible for angiogenesis of the allograft, that is, the formation of microvessels in transplant arteriosclerosis.
Key Words: transplantation • arteriosclerosis • angiogenesis • endothelium • lesion
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Circulation 2003 108: 3056-3058.
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