Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 234, Taiwan.
Division of Nephrology, Department of Medicine, Fu-Jen Catholic University Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 243, Taiwan.
Int J Mol Sci. 2020 Feb 1;21(3):980. doi: 10.3390/ijms21030980.
Vascular calcification (VC) is an important complication among patients of advanced age, those with chronic kidney disease, and those with diabetes mellitus. The pathophysiology of VC encompasses passive occurrence of physico-chemical calcium deposition, active cellular secretion of osteoid matrix upon exposure to metabolically noxious stimuli, or a variable combination of both processes. Epigenetic alterations have been shown to participate in this complex environment, through mechanisms including DNA methylation, non-coding RNAs, histone modifications, and chromatin changes. Despite such importance, existing reviews fail to provide a comprehensive view of all relevant reports addressing epigenetic processes in VC, and cross-talk between different epigenetic machineries is rarely examined. We conducted a systematic review based on PUBMED and MEDLINE databases up to 30 September 2019, to identify clinical, translational, and experimental reports addressing epigenetic processes in VC; we retrieved 66 original studies, among which 60.6% looked into the pathogenic role of non-coding RNA, followed by DNA methylation (12.1%), histone modification (9.1%), and chromatin changes (4.5%). Nine (13.6%) reports examined the discrepancy of epigenetic signatures between subjects or tissues with and without VC, supporting their applicability as biomarkers. Assisted by bioinformatic analyses blending in each epigenetic component, we discovered prominent interactions between microRNAs, DNA methylation, and histone modification regarding potential influences on VC risk.
血管钙化（VC）是高龄患者、慢性肾脏病患者和糖尿病患者的重要并发症。VC 的病理生理学包括物理化学钙沉积的被动发生、暴露于代谢毒性刺激时骨样基质的主动细胞分泌，或这两种过程的可变组合。表观遗传改变已被证明参与了这一复杂环境，其机制包括 DNA 甲基化、非编码 RNA、组蛋白修饰和染色质变化。尽管如此重要，但现有的综述未能提供所有相关报告的综合视图，这些报告涉及 VC 中的表观遗传过程，不同表观遗传机制之间的相互作用很少被检查。我们基于 PUBMED 和 MEDLINE 数据库进行了系统评价，截至 2019 年 9 月 30 日，以确定涉及 VC 中表观遗传过程的临床、转化和实验报告；我们检索到 66 项原始研究，其中 60.6%的研究着眼于非编码 RNA 的致病作用，其次是 DNA 甲基化（12.1%）、组蛋白修饰（9.1%）和染色质变化（4.5%）。有 9 项（13.6%）报告检查了有 VC 和无 VC 的受试者或组织之间表观遗传特征的差异，支持它们作为生物标志物的适用性。通过融合每个表观遗传成分的生物信息学分析，我们发现了 miRNA、DNA 甲基化和组蛋白修饰之间关于 VC 风险潜在影响的显著相互作用。
