Origin of neointimal endothelium and alpha-actin-positive smooth muscle cells in transplant arteriosclerosis
| Jazyk: | angličtina |
|---|---|
| Rok vydání: | 2001 |
| Předmět: | |
| Zdroj: | The Journal of Clinical Investigation. 107(11):1411-1422 |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | The development of transplant arteriosclerosis (TA) is today's most important problem in clinical organ transplantation. Hitologically, TA is characterized by perivascular inflammation and progressive intimal thickening. Current thought on this process of vascular remodeling assumes that neointimal vascular smooth muscle (VSM) cells and endothelium in TA are graft-derived, holding that medial VSM cells proliferate and migrate into the subendothelial spare in response to signals from inflammatory cells and damaged graft endothelium. Using MHC class I haplotype specific immunohistochemical staining and single-cell PCR analyses, we show that the neointimal alpha -actin-positive VSM cells in rat aortic or cardiac allografts are of recipient and not of donor origin. In aortic but not in cardiac allografts, recipient-derived endothelial cells (ECs) replaced donor endothelium. Cyclosporine treatment prevents neointima formation and preserves the vascular media in aortic allografts. Recipient-derived ECs do not replace graft endothelium after cyclosporine treatment. We propose that, although it progresses beyond the needs of functional repair, TA reflects the activity of a normal healing process that restores vascular wall function following allograft-induced immunological injury. |
| Databáze: | OpenAIRE |
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