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.

T cell costimulation blockade blunts pressure overload-induced heart failure / M. Kallikourdis, E. Martini, P. Carullo, C. Sardi, G. Roselli, C.M. Greco, D. Vignali, F. Riva, A.M. Ormbostad Berre, T.O. Stølen, A. Fumero, G. Faggian, E. Di Pasquale, L. Elia, C. Rumio, D. Catalucci, R. Papait, G. Condorelli. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 8:(2017 Mar). [10.1038/ncomms14680]

T cell costimulation blockade blunts pressure overload-induced heart failure

M. Kallikourdis
Primo
;
E. Martini
Secondo
;
C. Sardi;C.M. Greco;F. Riva;E. Di Pasquale;C. Rumio;G. Condorelli
Ultimo
2017-03

Abstract

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.
chemistry (all); biochemistry, genetics and molecular biology (all); physics and astronomy (all)
Settore VET/05 - Malattie Infettive degli Animali Domestici
Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/506220
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