Vemuganti Raghu, Dempsey Robert J
Department of Neurological Surgery, University of Wisconsin-Madison, Madison, Wisconsin 53792, USA.
J Neurochem. 2006 Apr;97 Suppl 1:92-6. doi: 10.1111/j.1471-4159.2005.03516.x.
The molecular mechanisms that render a carotid atherosclerotic plaque symptomatic have not yet been identified. Using an Affymetrix Human GeneChip set, we analyzed the gene expression patterns of 44 862 mRNA transcripts in surgically removed carotid artery plaques from six patients with symptomatic stroke and four non-symptomatic patients. The age, body mass index and the degree of stenosis were similar in the two groups. Some 236 transcripts (approximately 0.5% of the total transcripts analyzed) were expressed more abundantly in the symptomatic than the asymptomatic group. Of these, 61 transcripts are those that participate in ionic homeostasis, signal transduction and metabolism. The other groups of transcripts up-regulated in the symptomatic plaques include oncogenes, growth factors, tumor markers, angiogenesis promoters, transcription factors, and RNA splicing and processing factors. This study indicates that the higher metabolic activity in some atherosclerotic plaques leads to their faster growth and precipitation of stroke symptoms. The implications of these findings are that both diagnosis and prevention of stroke symptoms may become possible at the genetic level.
导致颈动脉粥样硬化斑块出现症状的分子机制尚未明确。我们使用Affymetrix人类基因芯片组,分析了6例有症状性卒中患者和4例无症状患者手术切除的颈动脉斑块中44862个mRNA转录本的基因表达模式。两组患者的年龄、体重指数和狭窄程度相似。约236个转录本(约占所分析转录本总数的0.5%)在有症状组中的表达比无症状组更为丰富。其中,61个转录本参与离子稳态、信号转导和代谢。在有症状斑块中上调的其他转录本组包括癌基因、生长因子、肿瘤标志物、血管生成促进因子、转录因子以及RNA剪接和加工因子。这项研究表明,一些动脉粥样硬化斑块中较高的代谢活性导致其更快生长并引发卒中症状。这些发现的意义在于,在基因水平上进行卒症状的诊断和预防或许成为可能。