Cell-free DNA Release in the Plasma of Patients with Cardiac Disease is Associated with Cell Death Processes

Junko Fujihara; Yoshikazu Takinami; Kaori Kimura-Kataoka; Yasuyuki Kawai; Haruo Takeshita

doi:10.1007/s12291-022-01034-y

Cell-free DNA Release in the Plasma of Patients with Cardiac Disease is Associated with Cell Death Processes

Indian J Clin Biochem. 2023 Jan;38(1):67-72. doi: 10.1007/s12291-022-01034-y. Epub 2022 Apr 21.

Authors

Junko Fujihara¹, Yoshikazu Takinami², Kaori Kimura-Kataoka¹, Yasuyuki Kawai³, Haruo Takeshita¹

Affiliations

¹ Department of Legal Medicine, Shimane University Faculty of Medicine, 89-1 Enya, 693-8501 Izumo, Shimane, Japan.
² Department of Emergency Medicine, Fukui Kosei Hospital, 201 Shimorokujyo, 918-8537 Fukui, Fukui Japan.
³ Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, 920-0293 Uchinada, Kanazawa, Ishikawa Japan.

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.

Keywords: Apoptosis; CyPA; M30; M65; MPO; NETosis; cfDNA.