Negative Correlation Between Secreted Phosphoprotein 1 and the Treg/Th17 Ratio in Non-Valvular Atrial Fibrillation

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia strongly associated with an imbalance between T helper 17 (Th17) cells and regulatory T cells (Treg). Secreted phosphoprotein 1 (SPP1), an immune signaling molecule implicated in AF pathogenesis, may shift the Th17/Treg cell balance in non-valvular AF (NVAF). This study aimed to explore the regulatory effects of SPP1 on the balance of Th17 and Treg cells in NVAF. Methods: Venous blood samples were collected from 58 patients with NVAF (observation group) and 58 age- and sex- matched healthy controls (control group). The serum concentrations of SPP1, along with the percentages of Treg and Th17 cells, and the levels of their associated cytokines, were measured. Correlation analysis was employed to evaluate the association between serum SPP1 levels and the Treg/Th17 cell ratio. In parallel, an experimental rat model of AF was established to investigate the expression of SPP1, related inflammatory factors, and fibrin within the left atrial tissue. Results: NVAF patients showed significantly higher serum levels of SPP1 and certain inflammatory cytokines (interleukin (IL)-17A and IL-23) than the controls. NVAF patients exhibited increased Th17 cells and elevated collagen I levels. Meanwhile, Treg cell frequency and IL-10 levels were significantly reduced compared to controls. Consequently, the Treg/Th17 ratio was significantly lower in NVAF patients. Notably, a significant inverse correlation was identified between serum SPP1 concentrations and the Treg/Th17 ratio. Consistent results were also obtained in animal models of AF, further supporting these findings. Conclusion: Our findings suggest that elevated SPP1 levels disrupt the Treg/Th17 cell balance in NVAF patients, promoting inflammation and fibrosis. These findings indicate that SPP1 represents a promising therapeutic target for the prevention and management of NVAF.