Tabibiazar Raymond, Wagner Roger A, Spin Joshua M, Ashley Euan A, Narasimhan Balasubramanian, Rubin Edward M, Efron Bradley, Tsao Phil S, Tibshirani Robert, Quertermous Thomas
Donald W. Reynolds Cardiovascular Clinical Research Center, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):302-8. doi: 10.1161/01.ATV.0000151372.86863.a5. Epub 2004 Nov 18.
Different strains of inbred mice exhibit different susceptibility to the development of atherosclerosis. The C3H/HeJ and C57Bl/6 mice have been used in several studies aimed at understanding the genetic basis of atherosclerosis. Under controlled environmental conditions, variations in susceptibility to atherosclerosis reflect differences in genetic makeup, and these differences must be reflected in gene expression patterns that are temporally related to the development of disease. In this study, we sought to identify the genetic pathways that are differentially activated in the aortas of these mice.
We performed genome-wide transcriptional profiling of aortas from C3H/HeJ and C57Bl/6 mice. Differences in gene expression were identified at baseline as well as during normal aging and longitudinal exposure to high-fat diet. The significance of these genes to the development of atherosclerosis was evaluated by observing their temporal pattern of expression in the well-studied apolipoprotein E model of atherosclerosis.
Gene expression differences between the 2 strains suggest that aortas of C57Bl/6 mice have a higher genetic propensity to develop inflammation in response to appropriate atherogenic stimuli. This study expands the repertoire of factors in known disease-related signaling pathways and identifies novel candidate genes for future study. To gain insights into the molecular pathways that are differentially activated in strains of mice with varied susceptibility to atherosclerosis, we performed comprehensive transcriptional profiling of their vascular wall. Genes identified through these studies expand the repertoire of factors in disease-related signaling pathways and identify novel candidate genes in atherosclerosis.
不同品系的近交系小鼠对动脉粥样硬化的发生表现出不同的易感性。C3H/HeJ和C57Bl/6小鼠已被用于多项旨在了解动脉粥样硬化遗传基础的研究中。在可控的环境条件下，对动脉粥样硬化易感性的差异反映了基因组成的差异，而这些差异必定体现在与疾病发生在时间上相关的基因表达模式中。在本研究中，我们试图确定在这些小鼠主动脉中差异激活的遗传途径。
我们对C3H/HeJ和C57Bl/6小鼠的主动脉进行了全基因组转录谱分析。在基线以及正常衰老和长期高脂饮食期间均鉴定出了基因表达的差异。通过观察它们在研究充分的动脉粥样硬化载脂蛋白E模型中的时间表达模式，评估了这些基因对动脉粥样硬化发生的意义。
这两个品系之间的基因表达差异表明，C57Bl/6小鼠的主动脉在受到适当的致动脉粥样硬化刺激时，具有更高的发生炎症的遗传倾向。本研究扩展了已知疾病相关信号通路中的因子库，并鉴定出了未来研究的新候选基因。为了深入了解在对动脉粥样硬化易感性不同的小鼠品系中差异激活的分子途径，我们对其血管壁进行了全面的转录谱分析。通过这些研究鉴定出的基因扩展了疾病相关信号通路中的因子库，并鉴定出了动脉粥样硬化中的新候选基因。
