Heart-specific DNA methylation analysis in plasma for the investigation of myocardial damage

Jie Ren; Lin Jiang; Xiaomeng Liu; Yuhan Liao; Xueyan Zhao; Fuchou Tang; Huimin Yu; Yibing Shao; Jizheng Wang; Lu Wen; Lei Song

doi:10.1186/s12967-022-03234-9

Heart-specific DNA methylation analysis in plasma for the investigation of myocardial damage

J Transl Med. 2022 Jan 21;20(1):36. doi: 10.1186/s12967-022-03234-9.

Authors

Jie Ren^#^{1

2

3}, Lin Jiang^#^{4

5}, Xiaomeng Liu^#^{1

6}, Yuhan Liao^{1

2}, Xueyan Zhao^{4

5}, Fuchou Tang^{1

2

3}, Huimin Yu⁷, Yibing Shao⁸, Jizheng Wang^{9

10}, Lu Wen^{11

12}, Lei Song^{13

14}

Affiliations

¹ Biomedical Pioneering Innovation Center, School of Life Sciences, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing, 100871, China.
² Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, 100871, China.
³ Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
⁴ State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100871, China.
⁵ National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100871, China.
⁶ Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
⁷ Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
⁸ Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong, China.
⁹ State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100871, China. jzwang@hotmail.com.
¹⁰ National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100871, China. jzwang@hotmail.com.
¹¹ Biomedical Pioneering Innovation Center, School of Life Sciences, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing, 100871, China. wenlu@pku.edu.cn.
¹² Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, 100871, China. wenlu@pku.edu.cn.
¹³ State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100871, China. songlqd@126.com.
¹⁴ National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100871, China. songlqd@126.com.

^# Contributed equally.

Abstract

Background: Circulating cell-free DNA (cfDNA) can be released when myocardial damage occurs.

Methods: Here, we used the methylated CpG tandem amplification and sequencing (MCTA-seq) method for analyzing dynamic changes in heart-derived DNA in plasma samples from myocardial infarction (MI) patients.

Results: We identified six CGCGCGG loci showing heart-specific hypermethylation patterns. MCTA-seq deconvolution analysis combining these loci detected heart-released cfDNA in MI patients at hospital admission, and showed that the prominently elevated total cfDNA level after percutaneous coronary intervention (PCI) was derived from both the heart and white blood cells. Furthermore, for the top marker CORO6, we developed a digital droplet PCR (ddPCR) assay that clearly detected heart damage signals in cfDNA of MI patients at hospital admission.

Conclusions: Our study provides insights into MI pathologies and developed a new ddPCR assay for detecting myocardial damage in clinical applications.

Keywords: Circulating cell-free DNA; DNA methylation; Myocardial infarction; Sequencing; ddPCR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell-Free Nucleic Acids* / genetics
DNA
DNA Methylation* / genetics
Humans
Percutaneous Coronary Intervention*
Polymerase Chain Reaction / methods

Substances

Cell-Free Nucleic Acids
DNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding