Abatacept significantly delayed the progression and decreased the severity of cardiac dysfunction in a mouse model of pressure overload-induced heart failure.
Does T cell costimulation blockade with abatacept reduce the progression and severity of cardiac dysfunction in a mouse model of pressure overload-induced heart failure?
T cell costimulation blockade with abatacept attenuates pressure overload-induced heart failure in mice, highlighting a potential novel immunomodulatory therapeutic strategy for HF.
Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF development in a mouse model of pathological cardiac hypertrophy and in human HF patients. T cell costimulation blockade, through FDA-approved rheumatoid arthritis drug abatacept, leads to highly significant delay in progression and decreased severity of cardiac dysfunction in the mouse HF model. The therapeutic effect occurs via inhibition of activation and cardiac infiltration of T cells and macrophages, leading to reduced cardiomyocyte death. Abatacept treatment also induces production of anti-inflammatory cytokine interleukin-10 (IL-10). IL-10-deficient mice are refractive to treatment, while protection could be rescued by transfer of IL-10-sufficient B cells. These results suggest that T cell costimulation blockade might be therapeutically exploited to treat HF.
Kallikourdis et al. (Mon,) conducted a other in Heart failure. Abatacept vs. PBS was evaluated on Cardiac dysfunction progression (Fractional shortening and Ejection fraction). Abatacept significantly delayed the progression and decreased the severity of cardiac dysfunction in a mouse model of pressure overload-induced heart failure.