DNA Methylation Profiling in Aneurysm and Comorbid Atherosclerosis of the Ascending Aorta

IF 1.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Biology Pub Date : 2024-06-05 DOI:10.1134/s0026893324700079

I. A. Goncharova, A. A. Zarubin, S. A. Shipulina, Iu. A. Koroleva, D. S. Panfilov, B. N. Kozlov, M. S. Nazarenko

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Abstract

Atherosclerosis and aneurysm of the aorta are relatively common pathological conditions that remain asymptomatic for a long period of time and have life-threatening and disabling complications. DNA methylation profiling in several regions (a dilated area, a nondilated area, and an atherosclerotic plaque) of the ascending aorta was carried out in patients with aortic aneurysm. DNA methylation was analyzed by reduced representation bisulfite sequencing (RRBS). Differences in methylation level between dilated and normal aortic tissues were detected for two CpG sites of the NR2F1-AS1 gene (|Δβ| ≥ 0.2 and FDR < 0.05). In total, 586/480 differentially methylated CpG sites (DMSs) were identified by comparing atherosclerotic plaque samples with dilated/normal aortic tissues; 323/234 of the DMSs were hypermethylated and 263/246 were hypomethylated in atherosclerotic plaques. Most DMSs were in introns and intergenic regions; 88.2% of the DMSs were in the binding sites of transcription factors, among which ZNf263, ZFP148, PATZ1, NRF1, TCF12, and EGR1 play a role in the pathogenesis of atherosclerosis of various arteries and ELK1, ETS1, and KLF15 play a role in aortic aneurysms. Sixteen DMSs were found in the regions of the genes CMIP, RPH3AL, XRCC1, GATA5, EXD3, KCNC2, HIVEP3, ADCY9, CDCP2, FOLR1, WT1, MGMT, GAS2, CA1, PRSS16, and ANK3, whose protein products are involved in both aortic dissection and atherosclerosis in various arterial circulation regions. The protein products of the genes are involved in a wide range of biological processes, including mesenchyme development (GO:0060485; FOLR1, WT1, GATA5, HIVEP3, and KCNC2) and positive regulation of DNA metabolic processes (GO:0051054; MGMT, WT1, and XRCC1).

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升主动脉动脉瘤和合并动脉粥样硬化的 DNA 甲基化图谱分析

摘要主动脉动脉粥样硬化和动脉瘤是一种比较常见的病理情况，长期无症状，并有危及生命和致残的并发症。研究人员对主动脉瘤患者升主动脉的几个区域（扩张区域、非扩张区域和动脉粥样硬化斑块）进行了DNA甲基化分析。通过还原表征亚硫酸氢盐测序（RRBS）分析了DNA甲基化情况。在 NR2F1-AS1 基因的两个 CpG 位点（|Δβ|≥ 0.2 和 FDR <0.05）上检测到扩张的主动脉组织和正常的主动脉组织之间甲基化水平的差异。通过比较动脉粥样硬化斑块样本和扩张/正常主动脉组织，共鉴定出586/480个差异甲基化CpG位点（DMSs）；在动脉粥样硬化斑块中，323/234个DMSs为高甲基化，263/246个DMSs为低甲基化。大多数 DMSs 位于内含子和基因间区域；88.2% 的 DMSs 位于转录因子的结合位点，其中 ZNf263、ZFP148、PATZ1、NRF1、TCF12 和 EGR1 在各种动脉粥样硬化的发病机制中起作用，ELK1、ETS1 和 KLF15 在主动脉瘤中起作用。在 CMIP、RPH3AL、XRCC1、GATA5、EXD3、KCNC2、HIVEP3、ADCY9、CDCP2、FOLR1、WT1、MGMT、GAS2、CA1、PRSS16 和 ANK3 等基因的区域发现了 16 个 DMSs，这些基因的蛋白产物参与了不同动脉循环区域的主动脉夹层和动脉粥样硬化。这些基因的蛋白产物参与多种生物过程，包括间质发育（GO:0060485；FOLR1、WT1、GATA5、HIVEP3 和 KCNC2）和 DNA 代谢过程的正向调节（GO:0051054；MGMT、WT1 和 XRCC1）。

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来源期刊

Molecular Biology 生物-生化与分子生物学

CiteScore

1.30

自引率

8.30%

发文量

审稿时长

3 months

期刊介绍： Molecular Biology is an international peer reviewed journal that covers a wide scope of problems in molecular, cell and computational biology including genomics, proteomics, bioinformatics, molecular virology and immunology, molecular development biology, molecular evolution and related areals. Molecular Biology publishes reviews, experimental and theoretical works. Every year, the journal publishes special issues devoted to most rapidly developing branches of physical-chemical biology and to the most outstanding scientists.