Comparative transcriptomic analysis of mice liver treated with different AMPK activators in a mice model of atherosclerosis.
Comparative transcriptomic analysis of mice liver treated with different AMPK activators in a mice model of atherosclerosis.
复制标题
在动脉粥样硬化小鼠模型中用不同 AMPK 激活剂治疗的小鼠肝脏的比较转录组分析
DOI：
10.18632/oncotarget.15027
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发表时间：
2017-03-07
期刊：
影响因子：
--
通讯作者：
Zhu H
中科院分区：
文献类型：
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作者：
Ma A;Wang D;An Y;Fang W;Zhu H
动脉粥样硬化是心血管疾病发生的主要潜在因素。抑制amp激活的蛋白激酶刺激动脉沉积多余的脂质，导致动脉粥样硬化病变的发展。在这项研究中，我们成功地建立了小鼠疾病模型，并模拟了治疗效果，为此我们选择了三种不同的amp激活蛋白激酶激活剂（IMM-H007， a -769662和Metformin），以确定哪种在动脉粥样硬化模型中具有更优的效果。我们将高脂饮食组和不同amp活化蛋白激酶激活剂处理的实验组四组小鼠肝脏转录组进行组合。我们分析了增加的基因以候选代谢和疾病途径。与高脂肪饮食组相比，治疗组共鉴定出799个差异表达基因。H007组、Metformin组和A-769662组分别有291、473和323个差异表达基因。H007组和二甲双胍组均观察到7条具有统计学意义的通路。我们期望小鼠模型中的基因表达谱将扩展我们在分子水平上对动脉粥样硬化的理解。该研究为今后人类动脉粥样硬化的临床研究提供了基础框架，并为开发治疗动脉粥样硬化的新药提供了新的线索。
Atherosclerosis is known to be the primary underlying factor responsible for the development of cardiovascular diseases. Suppression of AMP-activated protein kinase stimulates arterial deposition of excess lipids, resulting in the development of atherosclerotic lesions. In this study we successfully developed the disease model of mice and mimicked the therapeutic effect, for that we chose three different AMP-activated protein kinase activators (IMM-H007, A-769662 and Metformin) to identify which one has a superior effect in the atherosclerosis model. We combined the transcriptomes of four groups of mice liver including high-fat diet group and the experimental groups treated with different AMP-activated protein kinase activators. We analyzed the increased genes to candidate metabolic and disease pathways. Compared to the high-fat diet group, a total of 799 differentially expressed genes were identified in treatment groups. There were 291, 473, and 323 differentially expressed genes in H007, Metformin, and A-769662 group respectively. And seven statistically significant pathways were observed in both H007 and Metformin groups. We expect that gene expression profiling in the mice model would extend our understanding of atherosclerosis in the molecular level. This study provides a fundamental framework for future clinical research on human atherosclerosis and new clues for developing novel drugs for the treatment of atherosclerosis.