Extrachromosomal Circular DNA MIRECD Enhances Necroptosis and Predicts Prognosis of Myocardial Infarction

Recent researches have revealed the potential utility of extrachromosomal circular DNAs (eccDNAs) as biomarkers in various diseases. However, the association between plasma eccDNAs and myocardial infarction (MI) remains unclear. In this study, we extracted plasma eccDNA from blood samples of individ...

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Main Authors: Yiheng Zhao, Yujia Zhou, Shuchen Zhang, Boyang Xiang, Xiang Zhou
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2025-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0803
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author Yiheng Zhao
Yujia Zhou
Shuchen Zhang
Boyang Xiang
Xiang Zhou
author_facet Yiheng Zhao
Yujia Zhou
Shuchen Zhang
Boyang Xiang
Xiang Zhou
author_sort Yiheng Zhao
collection DOAJ
description Recent researches have revealed the potential utility of extrachromosomal circular DNAs (eccDNAs) as biomarkers in various diseases. However, the association between plasma eccDNAs and myocardial infarction (MI) remains unclear. In this study, we extracted plasma eccDNA from blood samples of individuals with acute MI and conducted Circle-Seq. We identified an MI-related eccDNA (MIRECD) with high expression levels in the plasma of patients with MI. Sanger sequencing validated its loop construction and sequence. Mechanistically, MIRECD could aggravate necroptosis via regulating the expression of mixed-lineage-kinase-domain-like pseudokinase (MLKL). Kaplan–Meier analysis demonstrated that the incidences of major adverse cardiac events (MACEs) and cardiovascular mortality were higher in individuals with elevated MIRECD levels. Univariate and multivariate Cox regression analyses indicated that MIRECD independently predicted the occurrence of MACEs in patients with MI. The addition of MIRECD enhanced the discrimination and reclassification ability compared with conventional risk factors. In conclusion, our study identified a novel eccDNA, MIRECD, which might regulate myocardial necroptosis through MLKL. MIRECD has the potential to serve as a reliable indicator for predicting the prognosis and stratifying the risk of MI.
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institution Kabale University
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publishDate 2025-01-01
publisher American Association for the Advancement of Science (AAAS)
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spelling doaj-art-93f1abfa6ef6405a8eae24e2b1ed99082025-08-20T03:40:52ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0803Extrachromosomal Circular DNA MIRECD Enhances Necroptosis and Predicts Prognosis of Myocardial InfarctionYiheng Zhao0Yujia Zhou1Shuchen Zhang2Boyang Xiang3Xiang Zhou4Department of Cardiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.Department of Cardiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.Department of Cardiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.Department of Cardiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.Recent researches have revealed the potential utility of extrachromosomal circular DNAs (eccDNAs) as biomarkers in various diseases. However, the association between plasma eccDNAs and myocardial infarction (MI) remains unclear. In this study, we extracted plasma eccDNA from blood samples of individuals with acute MI and conducted Circle-Seq. We identified an MI-related eccDNA (MIRECD) with high expression levels in the plasma of patients with MI. Sanger sequencing validated its loop construction and sequence. Mechanistically, MIRECD could aggravate necroptosis via regulating the expression of mixed-lineage-kinase-domain-like pseudokinase (MLKL). Kaplan–Meier analysis demonstrated that the incidences of major adverse cardiac events (MACEs) and cardiovascular mortality were higher in individuals with elevated MIRECD levels. Univariate and multivariate Cox regression analyses indicated that MIRECD independently predicted the occurrence of MACEs in patients with MI. The addition of MIRECD enhanced the discrimination and reclassification ability compared with conventional risk factors. In conclusion, our study identified a novel eccDNA, MIRECD, which might regulate myocardial necroptosis through MLKL. MIRECD has the potential to serve as a reliable indicator for predicting the prognosis and stratifying the risk of MI.https://spj.science.org/doi/10.34133/research.0803
spellingShingle Yiheng Zhao
Yujia Zhou
Shuchen Zhang
Boyang Xiang
Xiang Zhou
Extrachromosomal Circular DNA MIRECD Enhances Necroptosis and Predicts Prognosis of Myocardial Infarction
Research
title Extrachromosomal Circular DNA MIRECD Enhances Necroptosis and Predicts Prognosis of Myocardial Infarction
title_full Extrachromosomal Circular DNA MIRECD Enhances Necroptosis and Predicts Prognosis of Myocardial Infarction
title_fullStr Extrachromosomal Circular DNA MIRECD Enhances Necroptosis and Predicts Prognosis of Myocardial Infarction
title_full_unstemmed Extrachromosomal Circular DNA MIRECD Enhances Necroptosis and Predicts Prognosis of Myocardial Infarction
title_short Extrachromosomal Circular DNA MIRECD Enhances Necroptosis and Predicts Prognosis of Myocardial Infarction
title_sort extrachromosomal circular dna mirecd enhances necroptosis and predicts prognosis of myocardial infarction
url https://spj.science.org/doi/10.34133/research.0803
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AT shuchenzhang extrachromosomalcirculardnamirecdenhancesnecroptosisandpredictsprognosisofmyocardialinfarction
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