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T-bet deficiency attenuates cardiac remodelling in rats

  • Zhen-Guo Ma
  • Jia Dai
  • Yu-Pei Yuan
  • Zhou-Yan Bian
  • Si-Chi Xu
  • Ya-Ge Jin
  • Xin Zhang
  • Qi-Zhu Tang
Original Contribution
  • 210 Downloads

Abstract

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.

Keywords

T-bet Cardiac remodelling T lymphocytes T helper subset Interferon-γ 

Notes

Acknowledgements

This work was supported by Grants from the National Natural Science Foundation of China (Nos: 81270303, 81470516, 81470402, and 81700254) and the Key Project of the National Natural Science Foundation (No. 81530012) and the Fundamental Research Funds for the Central Universities (No. 2042017kf0085).

Compliance with ethical standards

Conflict of interest

The author(s) declare that they have no competing interests.

Supplementary material

395_2018_678_MOESM1_ESM.docx (2.1 mb)
Supplementary material 1 (DOCX 2115 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Zhen-Guo Ma
    • 1
    • 2
    • 3
  • Jia Dai
    • 1
    • 2
    • 3
  • Yu-Pei Yuan
    • 1
    • 2
    • 3
  • Zhou-Yan Bian
    • 1
    • 2
    • 3
  • Si-Chi Xu
    • 1
    • 2
    • 3
  • Ya-Ge Jin
    • 1
    • 2
    • 3
  • Xin Zhang
    • 1
    • 2
    • 3
  • Qi-Zhu Tang
    • 1
    • 2
    • 3
  1. 1.Department of CardiologyRenmin Hospital of Wuhan UniversityWuhanPeople’s Republic of China
  2. 2.Cardiovascular Research InstituteWuhan UniversityWuhanPeople’s Republic of China
  3. 3.Hubei Key Laboratory of CardiologyWuhanPeople’s Republic of China

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