Prevention of restenosis after PTCA by the requlation of Id, a trnscription factor of muscle differentiation.

本实验研究了血管平滑肌细胞（VSMC）的表型变化是否受Id蛋白的调控。Id蛋白是一种螺旋-环-螺旋型的无碱基区的转录蛋白。以大鼠Id cDNA为探针，采用北方Northern杂交技术检测VSMC中Id mRNA的表达。IdmRNA在大鼠主动脉组织中未检测到，但在培养的牛和人主动脉VSMC生长期明显增加。当细胞达到汇合时，Id mRNA表达显著降低至生长细胞的22%。还使用逆转录-聚合酶链反应检测了人直接冠状动脉粥样硬化斑块切除术样本中Id mRNA的表达。Id mRNA在PTCA后再狭窄病变中的表达率明显高于原发性动脉粥样硬化病变（67% vs.25%，p<0.05）。在5%胎牛血清（FBS）中加入30 μ M的Id反义寡脱氧核苷酸（ODN）可显著降低VSMC的生长（分别为28%和39%，p<0.01）。结果表明，Id表达与VSMC从收缩到增殖的表型变化密切相关，而与VSMC的趋化性无关，提示VSMC表型变化受螺旋-环-螺旋型反式作用因子的转录调控。

We examined whether the phenotypic change of vascular smooth muscle cells (VSMC) were regulated by Id protein, a helix-loop-helix type transcription without basic region. Id mRNA expression in VSMC was examined by Northern analysis using rat Id cDNA probe. Id mRNA,which was not detected in rat aortic tissue, was markedly increased in cultured VSMC from bovine and human aorta in growing phase. When cells reached confluency, Id mRNA expression was significantly reduced to 22% of growing cells. Id mRNA expression in human direct coronary atherectomy samples was also examined using reverse transcription-polymerase chain reaction. Id mRNA was detected predominantly in samples from restenotic lesion after PTCA compared to primary atherosclerotic lesion (67% vs.25%, p<0.05). VSMC growth in 5% fetal bovine serum (FBS) measured by 3H-thymidine uptake and cell number were markedly decreased by the addition of antisense oligodeoxyribo-nucleotides (ODN) to Id (30 muM) (28% and 39%, respectively, p<0.01). However, chemotactic activity of VSMC assessed by micro Boyden chamber method using 5% FCS as a chemoattractant was not reduced by Id antisense ODN.These results suggest that Id expression is closely-related to phenotype change of VSMC from contraction to proliferation but not to chemotaxis, and may suggest that the change in VSMC phenotype is transcriptionally regulated by helix-loop-helix type trans-acting factors.