Abstract 19152: Increased Extracellular Nucleosome Levels, Biomarkers of Cell Death, in Atrial Fibrillation Patients Compared to the Normal Population
Introduction: Atrial fibrillation (AF) is currently the most common cardiac arrhythmia encountered in clinical practice and a major cause of morbidity and mortality among adults. It is estimated that atrial fibrillation affects approximately 2.7 million people in the United States. Extracellular plasma nucleosomes (PNs) are complexes of DNA and histones that are released during cell death. Histones have been shown to function as DAMPs when they are translocated from the nucleus to the extracellular space. These nucleosomes mediate inflammatory and thromobotic responses and could serve as biomarkers in atrial fibrillation.
Methods: The concentration of PNs in plasma samples of atrial fibrillation patients (n=43), aged normals (n=35), and young normals (n=29) were measured using the Cell Death Detection ELISA PLUS assay (Roche Diagnostics, Mannheim, Germany). For this study, the baseline plasma samples of atrial fibrillation patients were analyzed.
Results: In comparison to the plasma from aged normals (11.42 ± 9.15 Arbitrary Units (AU)) and young normals (6.42 ± 0.87 AU; p < 0.0001), the plasma collected from atrial fibrillation patients (19.42 ± 20.5 AU; P = 0.0015) demonstrated much higher levels of PNs. When comparing the concentration of nucleosomes in plasma, the atrial fibrillation patients (306.1 ± 328.86 μg/mL) had much higher levels than the aged normals (177.9 ± 146.7 μg/mL; p = 0.0015).
Conclusion: PNs were elevated in atrial fibrillation when compared to both aged and young normals, indicating an increased release of nucleosomes, suggesting increased cell death. Extracellular nucleosomes function as DAMPs by binding to receptors and triggering the activation of multiple signal pathways. Due to the involvement of inflammation and thrombosis in the pathology of atrial fibrillation, the increased circulating nucleosome level in patients with atrial fibrillation implies that PNs may activate the immune system and generate the inflammatory response. These results suggest that PNs may serve as a biomarker in atrial fibrillation.
Author Disclosures: D. Hoppensteadt: None. S. Jabati: None. T. Phan: None. J. Liles: None. T. Rowe: None. J. Fareed: None. M. Syed: None.
- © 2016 by American Heart Association, Inc.