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C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload

  • Authors:
    • Xiaomin Wang
    • Wei Li
    • Qiang Yue
    • Wei Du
    • Yongming Li
    • Fu Liu
    • Liu Yang
    • Lijuan Xu
    • Ruiping Zhao
    • Jiang Hu
  • View Affiliations / Copyright

    Affiliations: Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China, Translational Medicine Center, Baotou Central Hospital, Donghe, Baotou 014040, P.R. China, Department of Cardiology, Baotou Central Hospital, Donghe, Baotou 014040, P.R. China, Department of Institution of Interventional and Vascular Surgery, Tongji University, Shanghai 200072, P.R. China, Baotou Central Hospital (The Post-doctoral Research Station of Clinic Medicine, Tongji University), Tongji University School of Medicine, Shanghai 200072, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 49
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    Published online on: November 13, 2020
       https://doi.org/10.3892/mmr.2020.11687
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Abstract

Aortic stenosis (AS) leads to chronic pressure overload, cardiac remodeling and eventually heart failure. Chemokines and their receptors have been implicated in pressure overload‑induced cardiac remodeling and dysfunction. In the present study, the role of C‑C chemokine receptor 5 (CCR5) in pressure overload‑induced cardiac remodeling and dysfunction was investigated in mice subjected to transverse aortic constriction (TAC). Cardiac levels of CCR5 and C‑C motif chemokine ligands (CCLs)3, 4 and 5 were determined by western blotting and reverse transcription‑quantitative PCR, respectively. Cardiac functional parameters were evaluated by echocardiographic and hemodynamic measurements. Myocardial fibrosis was assessed by Masson's trichrome staining and α‑smooth muscle actin immunostaining. Myocardial hypertrophy and inflammatory cell infiltration were evaluated by hematoxylin and eosin staining. Angiotensin II (Ang II)‑induced hypertrophy of H9c2 cardiomyocytes was assessed by F‑actin immunostaining. ERK1/2 and P38 phosphorylation was examined by western blotting. TAC mice exhibited higher myocardial CCL3, CCL4, CCL5 and CCR5 levels compared with sham mice. Compared with sham mice, TAC mice also exhibited impaired cardiac function along with myocardial hypertrophy, fibrosis and inflammatory cell infiltration. TAC‑induced cardiac remodeling and dysfunction were effectively ameliorated by administration of anti‑CCR5 but not by IgG control antibody. Mechanistically, increased ERK1/2 and P38 phosphorylation was detected in TAC hearts and Ang II‑stimulated H9c2 cardiomyocytes. Treatment with anti‑CCR5 antibody decreased ERK1/2 and P38 phosphorylation and attenuated Ang II‑induced H9c2 cell hypertrophy. CCR5 inhibition protected against pressure overload‑induced cardiac abnormality. The findings of the present study indicate that ERK1/2 and P38 signaling pathways may be involved in the cardioprotective effects of CCR5 inhibition.
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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Li W, Yue Q, Du W, Li Y, Liu F, Yang L, Xu L, Zhao R, Hu J, Hu J, et al: C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload. Mol Med Rep 23: 49, 2021.
APA
Wang, X., Li, W., Yue, Q., Du, W., Li, Y., Liu, F. ... Hu, J. (2021). C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload. Molecular Medicine Reports, 23, 49. https://doi.org/10.3892/mmr.2020.11687
MLA
Wang, X., Li, W., Yue, Q., Du, W., Li, Y., Liu, F., Yang, L., Xu, L., Zhao, R., Hu, J."C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload". Molecular Medicine Reports 23.1 (2021): 49.
Chicago
Wang, X., Li, W., Yue, Q., Du, W., Li, Y., Liu, F., Yang, L., Xu, L., Zhao, R., Hu, J."C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload". Molecular Medicine Reports 23, no. 1 (2021): 49. https://doi.org/10.3892/mmr.2020.11687
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Li W, Yue Q, Du W, Li Y, Liu F, Yang L, Xu L, Zhao R, Hu J, Hu J, et al: C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload. Mol Med Rep 23: 49, 2021.
APA
Wang, X., Li, W., Yue, Q., Du, W., Li, Y., Liu, F. ... Hu, J. (2021). C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload. Molecular Medicine Reports, 23, 49. https://doi.org/10.3892/mmr.2020.11687
MLA
Wang, X., Li, W., Yue, Q., Du, W., Li, Y., Liu, F., Yang, L., Xu, L., Zhao, R., Hu, J."C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload". Molecular Medicine Reports 23.1 (2021): 49.
Chicago
Wang, X., Li, W., Yue, Q., Du, W., Li, Y., Liu, F., Yang, L., Xu, L., Zhao, R., Hu, J."C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload". Molecular Medicine Reports 23, no. 1 (2021): 49. https://doi.org/10.3892/mmr.2020.11687
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