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Gene Expression Profile in the Early Stage of Angiotensin II-induced Cardiac Remodeling: a Time Series Microarray Study in a Mouse Model

机译:血管紧张素II诱导的心脏重构的早期阶段的基因表达谱:在小鼠模型中的时间序列微阵列研究。

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Background/Aims: Angiotensin II (Ang II) plays a critical role in the cardiac remodeling contributing to heart failure. However, the gene expression profiles induced by Ang II in the early stage of cardiac remodeling remain unknown. Methods: Wild-type male mice (C57BL/6 background, 10-weeek-old) were infused with Ang II (1500 ng/kg/min) for 7 days. Blood pressure was measured. Cardiac function and remodeling were examined by echocardiography, H&E and Masson staining. The time series microarrays were then conducted to detected gene expression profiles. Results: Microarray results identified that 1,489 genes were differentially expressed in the hearts at day 1, 3 and 7 of Ang II injection. These genes were further classified into 26 profiles by hierarchical cluster analysis. Of them, 4 profiles were significant (No. 19, 8, 21 and 22) and contained 904 genes. Gene Ontology showed that these genes mainly participate in metabolic process, oxidation-reduction process, extracellular matrix organization, apoptotic process, immune response, and others. Significant pathways included focal adhesion, ECM-receptor interaction, cytokine-cytokine receptor interaction, MAPK and insulin signaling pathways, which were known to play important roles in Ang II-induced cardiac remodeling. Moreover, gene co-expression networks analysis suggested that serine/cysteine peptidase inhibitor, member 1 (Serpine1, also known as PAI-1) localized in the core of the network. Conclusions: Our results indicate that many genes are mainly involved in metabolism, inflammation, cardiac fibrosis and hypertrophy. Serpine1 may play a central role in the development of Ang II-induced cardiac remodeling at the early stage.
机译:背景/目的:血管紧张素II(Ang II)在导致心脏衰竭的心脏重塑中起关键作用。然而,在心脏重构的早期由Ang II诱导的基因表达谱仍然是未知的。方法:向野生型雄性小鼠(C57BL / 6背景,10周龄)注入Ang II(1500 ng / kg / min)7天。测量血压。通过超声心动图,H&E和Masson染色检查心脏功能和重塑。然后进行时间序列微阵列检测基因表达谱。结果:芯片结果表明,在Ang II注射的第1、3和7天,心脏中有1489个基因差异表达。通过分级聚类分析将这些基因进一步分类为26个谱。其中,有4个显着特征(第19、8、21和22号),包含904个基因。基因本体论表明,这些基因主要参与代谢过程,氧化还原过程,细胞外基质组织,凋亡过程,免疫应答等。重要的途径包括粘着斑,ECM-受体相互作用,细胞因子-细胞因子受体相互作用,MAPK和胰岛素信号传导途径,已知这些途径在Ang II诱导的心脏重塑中起重要作用。此外,基因共表达网络分析表明,丝氨酸/半胱氨酸肽酶抑制剂成员1(Serpine1,也称为PAI-1)位于网络的核心。结论:我们的结果表明,许多基因主要与代谢,炎症,心脏纤维化和肥大有关。 Serpine1可能在早期由Ang II引起的心脏重塑的发展中发挥重要作用。

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