State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
Chin Med Sci J. 2020 Mar 31;35(1):43-53. doi: 10.24920/003709.
Objective Angiotensin Ⅱ (Ang Ⅱ)-induced vascular damage is a major risk of hypertension. However, the underlying molecular mechanism of AngⅡ-induced vascular damage is still unclear. In this study, we explored the novel mechanism associated with Ang II-induced hypertension. Methods We treated 8- to 12-week-old C57BL/6J male mice with saline and Ang Ⅱ(0.72 mg/kg·d) for 28 days, respectively. Then the RNA of the media from the collected mice aortas was extracted for transcriptome sequencing. Principal component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano plot. Functional annotations including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to reveal the molecular mechanism of Ang Ⅱ-induced hypertension. Finally, the differentially expressed genes were validated by using quantitative real-time PCR. Results The result revealed that a total of 773 genes, including 599 up-regulated genes and 174 down-regulated genes, were differentially expressed in the aorta of Ang Ⅱ-induced hypertension mice model. Functional analysis of differentially expressed genes manifested that various cellular processes may be involved in the Ang Ⅱ-induced hypertension, including some pathways associated with hypertension such as extracellular matrix, inflammation and immune response. Interestingly, we also found that the differentially expressed genes were enriched in vascular aging pathway, and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased (<0.05). Conclusion We identify that vascular aging is involved in Ang Ⅱ-induced hypertension, and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.
血管紧张素Ⅱ(Ang Ⅱ)诱导的血管损伤是高血压的主要风险因素。然而,AngⅡ诱导的血管损伤的潜在分子机制尚不清楚。在这项研究中,我们探索了与 AngⅡ诱导的高血压相关的新机制。
我们分别用生理盐水和 AngⅡ(0.72 mg/kg·d)处理 8-12 周龄 C57BL/6J 雄性小鼠 28 天。然后从收集的小鼠主动脉中提取中膜的 RNA 进行转录组测序。主成分分析用于显示不同样本的清晰分离,火山图显示差异表达基因的分布。功能注释包括基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径,以揭示 AngⅡ诱导的高血压的分子机制。最后,通过使用定量实时 PCR 验证差异表达基因。
结果表明,AngⅡ诱导的高血压小鼠模型主动脉中有 773 个基因差异表达,包括 599 个上调基因和 174 个下调基因。差异表达基因的功能分析表明,各种细胞过程可能参与 AngⅡ诱导的高血压,包括与高血压相关的一些途径,如细胞外基质、炎症和免疫反应。有趣的是,我们还发现差异表达基因富集在血管老化途径中,并进一步验证了胰岛素样生长因子 1 和脂联素的表达水平显著增加(<0.05)。
我们发现血管老化参与了 AngⅡ诱导的高血压,胰岛素样生长因子 1 和脂联素可能是导致血管老化的重要候选基因。