Ras基因对人股动脉平滑肌细胞增殖过程中基因表达的影响

Effect of Ras on gene expression profile during femoral artery smooth muscle cell proliferation

目的观察Ras基因对人股动脉平滑肌细胞增殖过程中基因表达的影响。方法以显性激活RAS基因和显性失活RAS基因重组腺病毒(AdRasV12和AdRasN17)转染人股动脉平滑肌细胞,采用Affymetrix基因芯片检测转染细胞的基因表达变化。结果转染AdRasN17后,120个基因表达发生显著变化,其中43个基因表达上调,77个基因表达下调。转染AdRasV12后,231个基因被确定为差异表达,其中127个基因表达上调,104个基因表达下调。这些基因功能主要与细胞周期和凋亡、信号转导、代谢和对刺激应答有关。结论激活和失活突变的Ras可改变人股动脉平滑肌细胞的基因表达,这些基因可能与动脉粥样硬化和再狭窄等心血管疾病发展过程中的动脉平滑肌细胞异常增殖有关。

Objective To investigate the effect of Ras on the gene expression during proliferation of human femoral artery smooth muscle cells. Methods Human femoral artery smooth muscle cells were transfected with recombinant adenovirusmediated active and negative mutants of Ras gene （ AdRasV12 and AdRasN17 respectively）, and the gene expression profile was determined by Affymetrix GeneChip. Results After transfection with AdRasN17, 120 genes were identified with significantly altered expression, among which 43 genes were up-regulated and 77 genes were down-regulated. While in counterparts of AdRasV12, 231 genes were identified as differentially expressed, among which 127 genes were up-regulated and 104 were down-regulated. These genes were functionally categorized as cell cycle and apoptosis categories, signal transduction, metabolism and response to stimulus. Conclusion The active and negative mutants of Ras may alter the gene expression of human femoral artery smooth muscle cells, and these gene targets may be involved in abnormal arterial smooth muscle cell proliferation in cardiovascular diseases such as atherosclerosis and restenosis.