Aikawa M, Yamaguchi H, Yazaki Y, Nagai R
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
J Atheroscler Thromb. 1995;2(1):14-23. doi: 10.5551/jat1994.2.14.
Smooth muscle myosin heavy chains (MHC) exist in multiple isoforms. Rabbit smooth muscle contain at least three types of MHC isoforms; SM1 (204 kDa), SM2 (200 kDa) and SMemb (200 kDa). SM1 and SM2 are specific to smooth muscle, but SMemb is a nonmuscle-type MHC abundantly expressed in the embryonic aorta and in activated mesenchymal cells. We previously reported that these three MHC isoforms are differentially expressed in rabbit during normal vascular development and in experimental arteriosclerosis and demonstrated that MHC isoforms are excellent markers for smooth muscle phenotype. In order to clarify the clinical significance of MHC isoforms, this article will focus on the expression of smooth muscle MHC isoforms in normally developing and atherosclerotic human arteries, especially in coronary arteries. We recently isolated and characterized three cDNA clones encoding human SM1, SM2, and SMemb. The expression of SM2 mRNA in the human fetal aorta was significantly lower as compared to SM1 mRNA but the ratio of SM2- to SM1-mRNA was increased after birth. SMemb mRNA in the aorta was decreased after birth. Immunohistologically, SM1 was constitutively positive from the fetal stage to adulthood in the apparently normal media of the aorta and coronary arteries, whereas SM2 was not detected in fetal arteries of early gestational stage. SM2 was recognized in well-differentiated smooth muscle after perinatal stage. In the human aorta or coronary arteries, unlike in rabbit, SMemb was detected even in the adult. Mild diffuse intimal thickening in the major coronary arteries of the young was found to be composed of smooth muscle cells, reacting equally to three antibodies for MHC isoforms. In thickened but non-atheromatous intima, the expression of well-differentiated smooth muscle-specific MHC (SM2) was reduced, especially in the deeper layer. With progression of atherosclerosis, intimal smooth muscle diminished the expression of not only SM2 but also SM1, whereas alpha-smooth muscle actin was well preserved. We conclude from these results that smooth muscle MHC isoforms are important molecular markers for studying human vascular smooth muscle cell differentiation as well as the cellular mechanisms of atherosclerosis.
平滑肌肌球蛋白重链（MHC）存在多种同工型。兔平滑肌至少含有三种MHC同工型；SM1（204 kDa）、SM2（204 kDa）和SMemb（200 kDa）。SM1和SM2是平滑肌特有的，但SMemb是一种非肌肉型MHC，在胚胎主动脉和活化的间充质细胞中大量表达。我们之前报道过，这三种MHC同工型在兔正常血管发育过程以及实验性动脉硬化过程中差异表达，并证明MHC同工型是平滑肌表型的优良标志物。为了阐明MHC同工型的临床意义，本文将聚焦于正常发育和动脉粥样硬化的人类动脉，尤其是冠状动脉中平滑肌MHC同工型的表达。我们最近分离并鉴定了三个编码人类SM1、SM2和SMemb的cDNA克隆。与SM1 mRNA相比，人胎儿主动脉中SM2 mRNA的表达显著较低，但出生后SM2与SM1 mRNA的比例增加。主动脉中SMemb mRNA在出生后减少。免疫组织化学显示，从胎儿期到成年期，在主动脉和冠状动脉明显正常的中膜中，SM1持续呈阳性，而在妊娠早期的胎儿动脉中未检测到SM2。围产期后，在分化良好的平滑肌中可识别出SM2。在人类主动脉或冠状动脉中，与兔不同，即使在成年人中也能检测到SMemb。在年轻人的主要冠状动脉中发现的轻度弥漫性内膜增厚由平滑肌细胞组成，对三种MHC同工型抗体的反应相同。在增厚但无动脉粥样硬化的内膜中，分化良好的平滑肌特异性MHC（SM2）表达降低，尤其是在较深层。随着动脉粥样硬化的进展，内膜平滑肌不仅减少了SM2的表达，也减少了SM1的表达，而α平滑肌肌动蛋白保存良好。从这些结果我们得出结论，平滑肌MHC同工型是研究人类血管平滑肌细胞分化以及动脉粥样硬化细胞机制的重要分子标志物。
