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Cell-free DNA Release in the Plasma of Patients with Cardiac Disease is Associated with Cell Death Processes
Junko Fujihara1, Yoshikazu Takinami2, Kaori Kimura-Kataoka1
1Department of Legal Medicine, Shimane University Faculty of Medicine, 89-1 Enya, 693-8501 Izumo, Shimane, Japan.
Insights
Cell-free DNA (cfDNA) in cardiac disease patients is elevated, primarily released by neutrophils via NETosis, not just apoptosis. Myocardial infarction (MI) patients show higher cfDNA levels, suggesting its diagnostic potential.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Biochemistry
Background:
- Cell-free DNA (cfDNA) circulates in plasma and its levels are altered in various diseases.
- Understanding the source and mechanism of cfDNA release in cardiac conditions is crucial for diagnostics.
Purpose of the Study:
- To investigate the source and mechanism of plasma cfDNA release in patients with myocardial infarction (MI) and other cardiac diseases.
- To correlate cfDNA levels with markers of apoptosis, necrosis, and neutrophil activation.
Main Methods:
- Assayed plasma cfDNA concentrations in 59 patients with cardiac diseases (including MI) and healthy controls.
- Measured plasma levels of apoptosis markers (M30, M65), necrosis marker (cyclophilin A - CyPA), and neutrophil activation marker (myeloperoxidase - MPO).
Main Results:
- Plasma cfDNA concentrations were significantly higher in cardiac disease patients (MI and others) compared to healthy controls.
- Myeloperoxidase (MPO) levels were significantly elevated in cardiac disease patients, with higher levels in MI patients than other cardiac diseases.
- No significant differences in M30, M65, or CyPA levels were observed among cardiac disease patients and controls.
Conclusions:
- Plasma cfDNA in cardiac disease patients is predominantly released by neutrophils through NETosis, alongside apoptosis, rather than solely epithelial apoptosis.
- Elevated cfDNA and MPO levels, particularly in MI patients, suggest their potential as diagnostic markers for myocardial infarction.
Abstract:
Cell-free DNA (cfDNA) is released into the plasma of patients with cardiac disease. Here, the source and mechanism of plasma cfDNA release in patients with myocardial infarction (MI) and other cardiac diseases (n = 59) were investigated. Plasma levels of various markers including M30 (apoptosis), M65 (apoptosis and necrosis), cyclophilin A (CyPA) (necrosis), and myeloperoxidase (MPO) (neutrophil activation) were assayed. The plasma cfDNA concentrations in MI and other cardiac diseases were significantly higher than that in the healthy control subjects. Significant differences were not observed among the cardiac disease patients (MI and other cardiac diseases) and healthy control subjects in M30, M65, and CyPA levels. In contrast,the MPO levels were significantly elevated in cardiac disease patients when compared to control groups, and MPO levels in MI patients were significantly higher than other cardiac diseases patients. These results suggest that cfDNA is mainly released by neutrophils via NETosis in addition to apoptosis except for epithelial apoptosis in patients with cardiac disease and the degree is greater in MI patients. The results from this study provide basic information for diagnosis marker of MI.
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