Pathogenesis and molecular mechanisms of arteral restenosis

我们先前证实兔和大鼠的平滑肌中至少含有三种类型的MHC：SM1(204 KDa)、SM2(200 KDa)和SMemb(200 KDa)。SM1和SM2是起源于单基因的两种平滑肌特异性MHC亚型，SMemb是第三种MHC亚型，在胚胎主动脉中大量表达。三种MHC亚型的表达受发育调控，血管平滑肌中存在发育调控的MHC亚型，为研究血管疾病的分子机制提供了重要的分子工具。我们首次证实，在经皮血管成形术(PTCA)后，增殖的平滑肌细胞发生肌球蛋白重链表达的发育调节；SMemb重新表达，SM2下调。因此，我们确定了SM1/2和SMemb基因的启动子区域。在本研究中，我们鉴定了SMemb基因的一个重要顺式元件和一个协同调节SMemb基因的转录因子BTEB-2，并进一步鉴定了SM1/2基因在平滑肌中的特异性表达。SM1/2基因在转录起始点上游含有两个CCTCCC元件-80bp。这些元件在SM1/2基因转录中起基础作用，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.