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T-bet deficiency attenuates cardiac remodelling in rats

Previous studies have suggested the involvement of CD4 + T lymphocytes in cardiac remodelling. T-bet can direct Th1 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...

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Bibliographic Details
Published in:Basic research in cardiology 2018-05, Vol.113 (3), p.19-12, Article 19
Main Authors: Ma, Zhen-Guo, Dai, Jia, Yuan, Yu-Pei, Bian, Zhou-Yan, Xu, Si-Chi, Jin, Ya-Ge, Zhang, Xin, Tang, Qi-Zhu
Format: Article
Language:English
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Summary:Previous studies have suggested the involvement of CD4 + T lymphocytes in cardiac remodelling. T-bet can direct Th1 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-γ (IFN-γ) 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-γ-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.
ISSN:0300-8428
1435-1803
DOI:10.1007/s00395-018-0678-x