在动脉样硬化中识别吸烟相关的内皮功能障碍的潜在枢纽基因和调控网络,使用生物信息学分析
Julong Guo1, Yachan Ning2, Dikang Pan1
1Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
概括
这项研究表明,吸烟会损害内皮细胞,这是动脉样硬化的关键因素. 生物信息学确定了232个常见基因和10个枢纽基因,包括HMOX1,为吸烟相关的血管功能障碍提供了潜在的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 生物信息学是一种生物信息学.
背景情况:
- 内皮功能障碍是动脉样硬化的早期迹象,通常是由吸烟引发的.
- 吸烟引起的内皮功能障碍背后的精确分子机制需要进一步阐明.
研究的目的:
- 用生物信息学研究动脉样硬化中吸烟相关的内皮功能障碍的分子机制.
- 为了确定参与这个过程的关键基因和途径.
主要方法:
- 利用基因表达综合 (GEO) 数据集 (GSE137578,GSE141136) 来识别因氧化低密度脂蛋白 (ox-LDL) 和烟草暴露而产生常见差异表达基因 (co-DEGs).
- 在共同DEGs上进行了基因本体学 (GO) 和基因和基因学京都百科全书 (KEGG) 路径丰富分析.
- 构建了一个蛋白质与蛋白质相互作用 (PPI) 网络以识别枢纽基因,并使用数据集GSE120521.1验证它们在不稳定的斑块中的表达.
- 预测的调节网络涉及非编码RNA和潜在的药物向枢纽基因.
主要成果:
- 鉴定了232个共同DEGs (113个上调,119个下调) 在自,细胞死亡,铁亡,脂质代谢,炎症和氧化应激等途径中丰富.
- 从PPI网络中选了10个枢纽基因,包括上调的FOS,HMOX1,SQSTM1,PTGS2,ATF3,DDIT3和下调的MCM4,KIF15,UHRF1,CCL2.
- 在不稳定的动脉样硬化斑块中证实了HMOX1的显著上调 (p=0.034).
- 建立了针对lncRNA/circRNA-miRNA-hub基因和药物-hub基因相互作用的监管网络.
结论:
- 吸烟引起的内皮损伤是动脉样硬化的一个重要因素.
- 生物信息学分析成功地确定了与吸烟相关的动脉样硬化内皮功能障碍的分子机制和潜在的治疗点.
- HMOX1和其他已识别的枢纽基因代表了未来治疗干预的有希望的目标.
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