Journal
BASIC RESEARCH IN CARDIOLOGY
Volume 113, Issue 3, Pages -Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-018-0678-x
Keywords
T-bet; Cardiac remodelling; T lymphocytes; T helper subset; Interferon-gamma
Categories
Funding
- National Natural Science Foundation of China [81270303, 81470516, 81470402, 81700254]
- Key Project of the National Natural Science Foundation [81530012]
- Fundamental Research Funds for the Central Universities [2042017kf0085]
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Previous studies have suggested the involvement of CD4 +T lymphocytes in cardiac remodelling. T-bet can direct Thl lineage commitment. This study aimed to investigate the functional significance of T-bet in cardiac remodelling induced by pressure overload using T-bet global knockout rats. Increased T-bet levels were observed in rodent and human hypertrophied hearts. T-bet deficiency resulted in a less severe hypertrophic phenotype in rats. CD4 + T-lymphocyte reconstitution in T-bet-/- rats resulted in aggravated cardiac remodelling. T-cell homing molecule expression and cytokine secretion were altered in T-bet-deficient rat hearts. Administration of exogenous interferon-gamma (IFN-gamma) offset T-bet deficiency-mediated cardioprotection. Cardiomyocytes cultured in T-bet-/- CD4 + T-cell-conditioned media showed a reduced hypertrophic response after hypertrophic stimuli, which was abolished by an IFN-gamma-neutralizing antibody. Taken together, our findings show that T-bet deficiency attenuates pressure overload-induced cardiac remodelling in rats. Specifically, targeting T-bet in T cells may be of great importance for the treatment of pathological cardiac remodelling and heart failure.
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