Programmed cell death-1 deficiency results in atrial remodeling in C57BL/6 mice

Deficiency of the programmed cell death-1 (PD-1) gene enhances T-cell activation and increases inflammation levels. It has been reported that atrial fibrillation (AF) is closely related to inflammation. The aim of the present study was to investigate the role of PD-1 deficiency in the pathogenesis of AF. Two groups of mice were used in our experiment: the C57BL/6 and the C57BL/6-PD-(1-/-) group. The expression of the inflammatory cytokines interleukin (IL)-2, -4, -6, -10, -17, interferon-γ and tumor necrosis factor were detected. Furthermore, the levels of atrial myocyte oxidative stress, the atrial effective refractory period (AERP) and the atrial myocardial fibrosis levels were determined. Compared with the C57BL/6 group, we found that the inflammatory cytokines were significantly increased in the PD-1(-/-) group and the levels of atrial myocyte oxidative stress in the PD-1(-/-) group were also higher. The AERP became shorter and the dispersion of AERP was increased in the PD-1(-/-) group. Moreover, the PD-1(-/-) group presented significant atrial myocardial fibrosis but the C57BL/6 group did not. Our findings strongly suggest that the higher levels of inflammatory cytokines and atrial myocyte oxidative stress were present in the PD-1(-/-) mice and resulted in atrial electricity and structural remodeling. Due to the atrial remodeling, the PD-1(-/-) mice were more likely to develop AF.