Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Circ J. 2010 Feb;74(2):233-9. doi: 10.1253/circj.cj-09-0809. Epub 2009 Dec 14.
Although 85,000 heart transplantations have been performed worldwide, coronary allograft vasculopathy (CAV), which is a phenomenon of chronic rejection, is still a serious problem. Because CAV involves all the allograft arteries, angioplasty, stenting or bypass grafting are not practical treatment options. Therefore, CAV is the biggest long-term limitation in cardiac allograft recipients. Although the cause of CAV is mostly immunologic, nonimmune pathways also contribute to its development. Several cytokines, chemokines and adhesion molecules play a critical role in the process. Cell adhesion, migration and proliferation of bone marrow progenitor and and other cells are involved in its development. Although there is not an established clinical strategy for preventing or treating CAV, recent investigations have provided some promising methodologies. Progress in DNA technology, such as antisense oligodeoxynucleotides (ODNs) to regulate the transcription of disease-related genes, has an important role in its therapeutic applications. Antisense ODN transfection preventing CAV in experimental cardiac allografts has been reported for the first time. The ODN strategy has not only been useful in the experimental studies, but is also a novel clinical strategy for gene therapy. The pathological and immunological characteristics of CAV and some promising methodologies for prevention of the disease are reviewed.
尽管全世界已经进行了 85000 例心脏移植手术，但冠状动脉移植血管病（CAV）作为一种慢性排斥反应现象仍然是一个严重的问题。由于 CAV 涉及所有移植动脉，因此血管成形术、支架置入或旁路移植术不是实际的治疗选择。因此，CAV 是心脏移植受者的最大长期限制因素。尽管 CAV 的病因主要是免疫性的，但非免疫途径也有助于其发展。几种细胞因子、趋化因子和黏附分子在该过程中发挥着关键作用。骨髓祖细胞和其他细胞的黏附、迁移和增殖参与了其发展。尽管目前还没有预防或治疗 CAV 的既定临床策略，但最近的研究提供了一些有前途的方法。DNA 技术的进步，如反义寡核苷酸（ODNs）来调节与疾病相关基因的转录，在其治疗应用中具有重要作用。反义 ODN 转染可预防实验性心脏同种异体移植中的 CAV 已首次报道。ODN 策略不仅在实验研究中有用，而且也是基因治疗的一种新的临床策略。本文综述了 CAV 的病理和免疫学特征，以及一些有前途的疾病预防方法。
