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

Ningxin Peng, Liqiong Guo, Zhonghai Wei, Xiao Wang, Lei Zhao, Lina Kang, Kun Wang, Weihong Zhou, Shoujun Cheng, Songjiang Yin, Biao Xu, Xue Bao

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number131606
JournalInternational Journal of Cardiology
DOIs
Publication statusAccepted/In press - 2023

Bibliographical note

Funding Information:
The authors thank all participants of the study and the staff of the Department of Cardiology of Nanjing Drum Tower Hospital and the Department of Health Management Center of Nanjing Drum Tower Hospital.

Funding Information:
The present study was funded by the Natural Science Foundation of Jiangsu Province (BK20200128 and BK20200842), the Nanjing Medical Science and Technology Development Project (YKK21070), the National Natural Science Foundation of China (82100478), and the Jiangsu Planned Projects for Postdoctoral Research Funds (2021K287B).

Publisher Copyright:
© 2023 Elsevier B.V.

Subject classification (UKÄ)

  • Cardiac and Cardiovascular Systems

Free keywords

  • Mitochondrial DNA methylation
  • Myocardial infarction
  • Platelet

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