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To date, chronic transplant dysfunction (CTD) is recognized as the major cause of long-term transplant loss (>1 year) after transplantation. CTD presents histologically with obliterated intragraft arteries as a result of intimal hyperplasia referred to as transplant arteriosclerosis (TA). Neointimal lesions predominantly consist of vascular smooth muscle cells (VSMCs) intermingled with some inflammatory cells. The pathogenesis of TA is believed to be multifactorial, and many risk factors have been identified. Because the precise pathogenetic mechanisms underlying TA are still largely unknown, adequate prevention and treatment protocols are not available. In this review, we discus the origin (donor vs recipient, bone marrow vs non-bone marrow) of neointimal endothelial cells (ECs) and VSMCs in TA lesions, which were formerly believed to be solely graft-derived. On the basis of the data obtained in both clinical and experimental transplantation, it appears that the process leading to TA is heterogeneous and that neointimal ECs and VSMCs can be recruited from different sources, possibly depending on the severity of vascular damage. These data suggest a significant role of host-derived circulating EC-VSMC progenitor cells, which may be partly bone marrow-derived. These circulating progenitor cells are potential targets for therapeutic intervention to ameliorate TA development or occlusive vascular disease in general. |
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