Pathogenesis and molecular mechanisms of arteral restenosis

我们之前已经证明，家兔和大鼠平滑肌包含至少三种类型的mhc；SM1(204kDa), SM2（200kDa）和SMemb（200kDa）。SM1和SM2是由单个基因产生的两种平滑肌特异性MHC异构体，SMemb是胚胎主动脉中大量表达的第三种MHC异构体。三种MHC亚型的表达受发育调控。在血管平滑肌中存在发育调节的MHC异构体，为研究血管疾病的分子机制提供了重要的分子工具。我们首先证明了肌球蛋白重链表达的发育调节发生在经皮血管成形术（PTCA）后增殖的平滑肌细胞中；SMemb重表达，SM2下调。因此，我们鉴定了SM1/2和SMemb基因的启动子区域。在这项研究中，我们确定了SMemb基因的一个重要顺式元件和一个转录因子BTEB-2，它们协调调节SMemb基因。我们进一步鉴定了SM1/2基因在平滑肌中最特异性表达。SM1/2基因包含两个CCTCCC元件，位于转录起始位点上游80 bp处。这些元件在SM1/2基因转录中发挥基本作用，但不一定调节平滑肌特异性表达。

We previously demonstrated that rabbit and rat smooth muscles contain at least three types of MHCs ; SM1(204kDa), SM2(200kDa)and SMemb(200kDa). SM1 and SM2 are two smooth muscle specific MHC isoforms arising from a singlegene, and SMemb is a third type of MHC isoform abundantly expressed in embryonic aortas. The expression of three MHC isoforms is developmentallyregulated.The presence of developmentallyregulated MHC isoforms in vascular smooth muscles provides importantmoleculartools to investigate the molecularmechanism underlying vascular diseases. We first demonstrated that the developmentalregulation of myosin heavy chain expression occurs in proliferating smooth muscle cells after percutaneous angioplasty(PTCA) ; SMemb was reexpressed and SM2 was downregulated. We therefore characterized the promoter region of the SM1/2 and SMemb genes. In this study, we identified an important cis element for the SMemb gene and a transcription factor, BTEB-2, which coordinately regulate the SMemb gene.We furthermore characterized SM1/2 gene which is most specifically expressed in smooth muscles. SM1/2 gene harbors two CCTCCC elements-80 bp upstream of the transcription initiation site. These elements play a basic role for SM1/2 gene transcription but does not necessarily regulate smooth muscle-specific expression.