血小板线粒体 DNA 甲基化：心肌梗死的一种新型生物标志物——初步研究。

Platelet mitochondrial DNA methylation: A novel biomarker for myocardial infarction - A preliminary study.

机构信息

Department of Cardiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, China; Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou, China.

出版信息

Int J Cardiol. 2024 Mar 1;398:131606. doi: 10.1016/j.ijcard.2023.131606. Epub 2023 Nov 22.

DOI:10.1016/j.ijcard.2023.131606

PMID:37996014

Abstract

BACKGROUND

Platelet activation and thrombus formation play critical roles in the pathogenesis of myocardial infarction (MI). In addition to their role in energy production, platelet mitochondria also regulate cellular functions related to apoptosis, oxidative stress, and inflammation. Epigenetic modifications of platelet mitochondrial DNA (mtDNA) may influence platelet function and are believed to be an important factor in MI. Therefore, the aim of this study was to investigate the differences in platelet mtDNA methylation levels between MI patients and controls.

METHODS

The present study utilized propensity score matching to generate 45 multivariate matched apparently healthy controls for 45 patients with newly-onset acute MI. Platelet mtDNA methylation levels were assessed through bisulfite-PCR pyrosequencing and compared between the two groups, with further adjustments made in the sensitivity analysis.

RESULTS

Among the measured mitochondrial genes (MT-COX1, MT-COX2, MT-COX3, MT-ND5, MT-ATP6 and tRNA_Leu), patients with MI exhibited statistically significant differences in mtDNA methylation levels as compared to matched controls. Specifically, higher levels of mtDNA methylation were observed in MT-COX1, MT-COX3, and tRNA_Leu, while a lower level was observed in MT-ATP6 (all p < 0.0001). These results remained robust in the sensitivity analysis.

CONCLUSION

Our study demonstrated significant variations in platelet mtDNA methylation levels between patients with MI and controls. Platelet mtDNA methylation may serve as a novel biomarker for MI. This observation also provided some insights into the etiology of MI.

摘要

背景

血小板激活和血栓形成在心肌梗死（MI）的发病机制中起着关键作用。除了在能量产生中的作用外，血小板线粒体还调节与细胞凋亡、氧化应激和炎症相关的细胞功能。血小板线粒体 DNA（mtDNA）的表观遗传修饰可能影响血小板功能，被认为是 MI 的一个重要因素。因此，本研究旨在探讨 MI 患者和对照组之间血小板 mtDNA 甲基化水平的差异。

方法

本研究采用倾向评分匹配生成 45 例新发生急性 MI 患者和 45 例多变量匹配的貌似健康对照者。通过亚硫酸氢盐-PCR 焦磷酸测序评估血小板 mtDNA 甲基化水平，并在敏感性分析中进行进一步调整。

结果

在所测量的线粒体基因（MT-COX1、MT-COX2、MT-COX3、MT-ND5、MT-ATP6 和 tRNA_Leu）中，与匹配的对照组相比，MI 患者的 mtDNA 甲基化水平存在统计学差异。具体而言，MT-COX1、MT-COX3 和 tRNA_Leu 的 mtDNA 甲基化水平较高，而 MT-ATP6 的水平较低（均 P<0.0001）。这些结果在敏感性分析中仍然稳健。