血管转录组测序发现血管紧张素2诱导的高血压小鼠动脉组织衰老相关基因改变

吕双杰; 丁杨楠; 裴小雅; 赵翔; 郝德龙; 张祝琴; 陈厚早; 刘德培

doi:10.24920/003709

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血管转录组测序发现血管紧张素2诱导的高血压小鼠动脉组织衰老相关基因改变

中国医学科学杂志（英文版） 2020年35卷第1期页码：43-53

Original Article | Updated：2024-04-10

- 血管转录组测序发现血管紧张素2诱导的高血压小鼠动脉组织衰老相关基因改变
- Affiliations：
  
  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
- Author bio：
  
  * Houzao Chen, E-mail: chenhouzao@ibms.cams.cn。
  Depei Liu, liudp@pumc.edu.cn
- Funds：
- DOI：10.24920/003709
  中图分类号：
- 收稿日期：2019-01-15，
  
  网络出版日期：2020-03-31，
  
  纸质出版日期：2020-03-16
- Accepted：
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吕双杰, 丁杨楠, 裴小雅, 等. 血管转录组测序发现血管紧张素2诱导的高血压小鼠动脉组织衰老相关基因改变[J]. 中国医学科学杂志（英文版）, 2020,35(1):43-53.

Lv Shuangjie, Ding Yangnan, Pei Xiaoya, et al. Vascular Transcriptome Profiling Reveals Aging-Related Genes in Angiotensin Ⅱ-Induced Hypertensive Mouse Aortas[J]. Chinese medical sciences journal, 2020, 35(1): 43-53.
吕双杰, 丁杨楠, 裴小雅, 等. 血管转录组测序发现血管紧张素2诱导的高血压小鼠动脉组织衰老相关基因改变[J]. 中国医学科学杂志（英文版）, 2020,35(1):43-53. DOI： 10.24920/003709.

Lv Shuangjie, Ding Yangnan, Pei Xiaoya, et al. Vascular Transcriptome Profiling Reveals Aging-Related Genes in Angiotensin Ⅱ-Induced Hypertensive Mouse Aortas[J]. Chinese medical sciences journal, 2020, 35(1): 43-53. DOI： 10.24920/003709.

摘要

目的

血管紧张素2诱导的血管损伤是高血压的主要危险之一。可是

我们对于血管紧张素2诱导的血管损伤的潜在分子机制仍不清楚。在本研究中

我们旨在探索血管紧张素2诱导高血压的新机制。

方法

8到12周龄的雄性C57BL/6J小鼠分别用生理盐水和血管紧张素2（0.72 mg/kg·d）处理28天

提取小鼠动脉RNA进行转录组测序。采用主成分分析证实不同处理的样本的可区分性

火山图展示差异表达基因的分布情况。通过GO和KEGG通路分析研究差异表达基因的功能。此外

通过实时荧光定量聚合酶链式反应（qRT-PCR）验证转录组测序结果中部分差异表达基因的表达水平。

结果

在血管紧张素2诱导的高血压小鼠模型的动脉中

共有773个基因表达发生了显著性改变

包括599个上调基因和174个下调基因。通过对差异表达基因的功能分析发现不同的细胞过程可能参与了血管紧张素2诱导的高血压过程

包括一些已知的与高血压密切相关的通路

如细胞外基质

炎症和免疫反应。此外

我们发现差异表达基因主要富集于血管衰老通路

qRT-PCR证实其中胰岛素类生长因子1和脂联素基因表达显著上调（P

0.05）。

结论

血管衰老和血管紧张素2诱导的高血压相关

胰岛素类生长因子1和脂联素可能是导致血管衰老的重要候选基因。

Abstract

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.

关键词

Keywords

references

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