Suzuki J, Isobe M, Aikawa M, Kawauchi M, Shiojima I, Kobayashi N, Tojo A, Suzuki T, Kimura K, Nishikawa T, Sakai T, Sekiguchi M, Yazaki Y, Nagai R
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Circulation. 1996 Sep 1;94(5):1118-24. doi: 10.1161/01.cir.94.5.1118.
Diagnosis of acute rejection and graft arteriosclerosis (chronic rejection) is critical to the success of cardiac transplantation, but accurate diagnosis is often difficult. We have reported that there are three types of vascular myosin heavy chain (MHC) isoforms: SM1, SM2, and SMemb. SM2 is specifically expressed in differentiated smooth muscle cells (SMCs). SMemb is a nonmuscle-type MHC abundantly expressed in SMCs of fetal aorta.
To evaluate the usefulness of MHC expression for diagnosis and analysis of acute and chronic rejection, heterotopic cardiac transplantation was performed in rats and monkeys. Immunohistochemistry, electron microscopy, and Northern blot assay were performed to evaluate MHC expression. SMemb was expressed in spindle-shaped cells located in acutely rejected myocardium in the rats and monkeys. These cells were also observed in areas lacking cellular infiltration. These SMemb-positive cells were activated fibroblasts or myofibroblasts. SMemb mRNA was enhanced parallel to the progression of acute rejection. In the coronary arteries of chronically rejected allografts, enhanced SMemb and reduced SM2 expression was observed in both thickened intima and media. The reduced medial SM2 expression was observed before the intimal thickening occurred. These cells were phenotypically modulated SMCs.
Altered expression of MHC isoforms is a sensitive indicator in the diagnosis of acute and chronic cardiac rejection. The pathophysiology of this alteration in MHC isoform expression should be studied further to elucidate the pathogenesis of cardiac rejection.
急性排斥反应和移植血管硬化（慢性排斥反应）的诊断对于心脏移植的成功至关重要，但准确诊断往往困难。我们曾报道存在三种血管肌球蛋白重链（MHC）亚型：SM1、SM2和SMemb。SM2在分化的平滑肌细胞（SMC）中特异性表达。SMemb是一种非肌肉型MHC，在胎儿主动脉的SMC中大量表达。
为评估MHC表达在急性和慢性排斥反应诊断及分析中的作用，在大鼠和猴子中进行了异位心脏移植。采用免疫组织化学、电子显微镜和Northern印迹分析来评估MHC表达。在大鼠和猴子急性排斥的心肌中，位于梭形细胞中的SMemb表达。在缺乏细胞浸润的区域也观察到这些细胞。这些SMemb阳性细胞是活化的成纤维细胞或肌成纤维细胞。SMemb mRNA随着急性排斥反应的进展而增强。在慢性排斥的同种异体移植物的冠状动脉中，在内膜和中膜增厚处均观察到SMemb增强和SM2表达减少。在内膜增厚发生之前就观察到中膜SM2表达减少。这些细胞是表型调节的SMC。
MHC亚型表达的改变是急性和慢性心脏排斥反应诊断中的敏感指标。应进一步研究MHC亚型表达这种改变的病理生理学，以阐明心脏排斥反应的发病机制。
