Gene expression profiles of mouse aorta and cultured vascular smooth muscle cells differ widely, yet show common responses to dioxin exposure.
Gene expression profiles of mouse aorta and cultured vascular smooth muscle cells differ widely, yet show common responses to dioxin exposure.
复制标题
DOI：
10.1385/ct:4:4:385
复制
发表时间：
2004-01-01
影响因子：
3.2
通讯作者：
Medvedovic, Mario
中科院分区：
文献类型：
--
作者：
Puga, Alvaro;Sartor, Maureen A;Medvedovic, Mario
暴露于环境毒物可能在心血管疾病的发生和发展中起作用。许多环境因素，如二恶英，是动脉粥样硬化的危险因素，因为它们可能通过改变基因表达模式来加剧潜在的疾病。血管组织的表达谱允许同时分析数千个基因，并可提供在早期疾病阶段特别有用的预测信息。然而，由于材料或伦理原因，体内实验通常是不可行的，必须使用培养细胞的数据，即使可能不知道培养细胞和活组织是否对相同的毒物有共同的整体反应。在寻找对二恶英暴露有反应的基因时，我们使用具有来自13，433个基因的DNA序列的寡核苷酸微阵列来比较C57 BL/6小鼠睾丸与培养的相同小鼠的血管平滑肌细胞（vSMC）的全局基因表达谱。主动脉节段和vSMC在超过4500个基因的表达上存在差异，许多基因的表达差异超过1000倍。将微阵列数据整合到基因本体论项目注释中表明，许多差异表达的基因属于相同的生物过程或代谢途径。尽管有这些结果，一个子集的35个基因以相同的方式在两个系统中二恶英暴露的反应。该亚群中的基因编码I相和II相解毒酶、信号转导激酶和磷酸酶以及参与DNA修复和细胞周期的蛋白质。我们的结论是，vSMCS可能是有用的主动脉替代品，研究早期基因表达反应二恶英暴露，分析集中在这个子集的基因。
Exposure to environmental toxicants may play a role in the onset and progression of cardiovascular disease. Many environmental agents, such as dioxin, are risk factors for atherosclerosis because they may exacerbate an underlying disease by altering gene expression patterns. Expression profiling of vascular tissues allows the simultaneous analysis of thousands of genes and may provide predictive information particularly useful in early disease stages. Often, however, in vivo experiments are unfeasible for material or ethical reasons, and data from cultured cells must be used instead, even though it may not be known whether cultured cells and live tissues share common global responses to the same toxicant. In a search for genes responsive to dioxin exposure, we used oligonucleotide microarrays with DNA sequences from 13,433 genes to compare global gene expression profiles of C57BL/6 mice aortas with cultured vascular smooth muscle cells (vSMCs) of the same mice. Aorta segments and vSMCs differed in the expression of more than 4500 genes, many showing expression differences greater than 1000-fold. Integration of microarray data into Gene Ontology Project annotations showed that many of the genes differentially expressed belonged to the same biological process or metabolic pathway. Notwithstanding these results, a subset of 35 genes responded in the same fashion to dioxin exposure in both systems. Genes in this subset encoded phase I and phase II detoxification enzymes, signal transduction kinases and phosphatases, and proteins involved in DNA repair and the cell cycle. We conclude that vSMCS may be useful aorta surrogates to study early gene expression responses to dioxin exposure, provided that analyses focus on this subset of genes.