King's College London, London, UK.
J Heart Lung Transplant. 2010 Jul;29(7):792-9. doi: 10.1016/j.healun.2010.03.005. Epub 2010 Apr 24.
Coronary allograft vasculopathy (CAV) is the major limiting factor for long term survival after heart transplantation. The aim of this study was to identify gene candidates implicated in human CAV using a rat aortic allograft model in tandem with microarrays and quantitative real time PCR (Q-PCR).
Rat abdominal aortas were isografted (5) or allografted (5) from Brown-Norway to Lewis rats and grafts were harvested after day 8, 25 and 60. Agilent microarrays were then used to highlight differentially expressed genes between isografted and allografted rat aortas. Further investigation of a selected candidate gene was performed on human coronary arteries.
1829, 2582 and 1925 genes (fold changes >2 or <2 and p values <0.05) were differentially expressed at day 8, 25 and 60 respectively between isografs and allografts. Seventeen candidate genes were selected according to significant differential expression at day 60. These rat candidate genes were then validated by quantitative real time polymerase chain reaction (Q-PCR). One of these candidate genes, T-Cadherin (T-Cad) was further investigated, using immunohistochemistry (IHC), in human coronary arteries showing CAV compared to classical atherosclerosis present in ischemic cardiomyopathy (ICM) and normal coronary arteries present in dilated cardiomyopathy (DCM). Results showed an over expression of T-Cad in CAV and classical atherosclerosis compared to normal coronary arteries.
T-Cad was found to be over expressed in CAV. T-Cad could potentially act as a trigger for smooth muscle cells (SMCs) proliferation and vascular remodelling observed in CAV leading to a diffuse narrowing of the arterial lumen.
冠状动脉移植血管病（CAV）是心脏移植后长期生存的主要限制因素。本研究旨在使用大鼠主动脉同种异体移植模型与微阵列和定量实时 PCR（Q-PCR）相结合，鉴定与人类 CAV 相关的基因候选者。
Brown-Norway 大鼠的腹部主动脉被同种移植（5 个）或同种异体移植（5 个）到 Lewis 大鼠，移植后第 8、25 和 60 天采集移植物。然后使用安捷伦微阵列突出同种和同种异体大鼠主动脉之间差异表达的基因。对选定的候选基因在人类冠状动脉中的进一步研究。
分别在第 8、25 和 60 天，同种和同种异体之间有 1829、2582 和 1925 个基因（倍数变化>2 或<2 和 p 值<0.05）差异表达。根据第 60 天的显著差异表达选择了 17 个候选基因。这些大鼠候选基因随后通过定量实时聚合酶链反应（Q-PCR）进行验证。其中一个候选基因，T-钙粘蛋白（T-Cad）在人冠状动脉中的免疫组织化学（IHC）中进一步研究，与缺血性心肌病（ICM）中存在的经典动脉粥样硬化和扩张型心肌病（DCM）中存在的正常冠状动脉相比，CAV 显示出 T-Cad 的过表达。结果表明，与正常冠状动脉相比，T-Cad 在 CAV 和经典动脉粥样硬化中表达过度。
T-Cad 在 CAV 中表达过度。T-Cad 可能作为平滑肌细胞（SMC）增殖和 CAV 中观察到的血管重塑的触发因素，导致动脉管腔弥漫性变窄。
