Hillebrands Jan-Luuk, Rozing Jan
Department of Cell Biology, Immunology Section, Faculty of Medical Sciences, University of Groningen, MWF bldg 3215, A. Deusinglaan 1, NL-9713 AV, Groningen, The Netherlands.
Expert Rev Mol Med. 2003 Jan 13;5(2):1-23. doi: 10.1017/S146239940300557X.
Although effective in the short-term, clinical solid-organ transplantation has not achieved its goals as a long-term treatment for patients with end-stage organ failure. Development of so-called chronic transplant dysfunction (CTD)is now recognised as the predominant cause of allograft loss long-term (after the first post-operative year) following transplantation. CTD has the remarkable histological feature that the luminal areas of intragraft arteries become obliterated, predominantly with vascular smooth muscle cells intermingled with some inflammatory cells. The development of this transplant vasculopathy,referred to as transplant arteriosclerosis (TA), is a multifactorial process and many risk factors have been identified. However, the precise pathogenetic mechanisms leading to TA are largely unknown and, as a result, current prevention and treatment protocols are inadequate. This review discusses the risk factors for TA and current views on the pathogenetic mechanisms leading to this vasculopathy. We argue here that host-derived cells contribute to the development of these vascular lesions, and propose that TA results from a normal vascular repair process that proceeds beyond the needs of functional repair. Guided by the proposed sequence of events, we finally discuss possible directions for future intervention strategies to prevent TA after solid-organ transplantation.
尽管临床实体器官移植在短期内有效，但作为终末期器官衰竭患者的长期治疗方法，尚未实现其目标。所谓的慢性移植功能障碍（CTD）的发展现在被认为是移植后长期（术后第一年之后）同种异体移植物丢失的主要原因。CTD具有显著的组织学特征，即移植物内动脉的管腔区域闭塞，主要是血管平滑肌细胞与一些炎症细胞混合。这种移植血管病变的发展，称为移植动脉硬化（TA），是一个多因素过程，已经确定了许多危险因素。然而，导致TA的确切发病机制在很大程度上尚不清楚，因此，目前的预防和治疗方案并不充分。本综述讨论了TA的危险因素以及导致这种血管病变的发病机制的当前观点。我们在此认为宿主来源的细胞促成了这些血管病变的发展，并提出TA是由超出功能修复需要的正常血管修复过程导致的。根据所提出的事件顺序，我们最后讨论了实体器官移植后预防TA的未来干预策略的可能方向。
