Open Access

Ablation of CXCR4 expression in cardiomyocytes exacerbates isoproterenol‑induced cell death and heart failure

  • Authors:
    • Min Cheng
    • Can Chen
    • Kunwu Yu
    • Xiao Lv
    • Qiutang Zeng
    • Nianguo Dong
    • Feng Zhu
  • View Affiliations

  • Published online on: December 29, 2022     https://doi.org/10.3892/ijmm.2022.5216
  • Article Number: 13
  • Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

CXCR4 is a seven‑transmembrane‑spanning Gi‑coupled receptor for the SDF‑1 chemokine and plays a critical role in cardiovascular development and post‑injury repair. However, the specific role of CXCR4 in cardiomyocytes is incompletely understood. It was hypothesized that CXCR4 activation in cardiomyocytes antagonizes β‑adrenoceptor/Gs signaling‑induced cardiac dysfunction. Cardiomyocyte‑specific CXCR4 knockout (CXCR4‑CMKO) mice were generated by crossing CXCR4fl/fl and MHC‑Cre+/‑ mice. Their cardiac structure and function in the basal state are equivalent to that of the control MHC‑Cre+/‑ littermates until at least 4 months old. However, following continuous subcutaneous administration of isoproterenol (Iso) via an osmotic mini‑pump, the ventricular myocardial contractility, dilation, cardiomyocyte apoptosis, and interstitial fibrosis are worse in CXCR4‑CMKO mice than in MHC‑Cre+/‑ littermates. In the cultured H9C2 cardiomyocytes, SDF‑1 treatment markedly attenuated Iso‑induced apoptosis and reduction in phospho‑Akt, and this protective effect was lost by knockdown of CXCR4 or by co‑treatment with Gi inhibitors. In conclusion, CXCR4 promotes cardiomyocyte survival and heart function during β‑adrenergic stress.
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February-2023
Volume 51 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Cheng M, Chen C, Yu K, Lv X, Zeng Q, Dong N and Zhu F: Ablation of CXCR4 expression in cardiomyocytes exacerbates isoproterenol‑induced cell death and heart failure. Int J Mol Med 51: 13, 2023
APA
Cheng, M., Chen, C., Yu, K., Lv, X., Zeng, Q., Dong, N., & Zhu, F. (2023). Ablation of CXCR4 expression in cardiomyocytes exacerbates isoproterenol‑induced cell death and heart failure. International Journal of Molecular Medicine, 51, 13. https://doi.org/10.3892/ijmm.2022.5216
MLA
Cheng, M., Chen, C., Yu, K., Lv, X., Zeng, Q., Dong, N., Zhu, F."Ablation of CXCR4 expression in cardiomyocytes exacerbates isoproterenol‑induced cell death and heart failure". International Journal of Molecular Medicine 51.2 (2023): 13.
Chicago
Cheng, M., Chen, C., Yu, K., Lv, X., Zeng, Q., Dong, N., Zhu, F."Ablation of CXCR4 expression in cardiomyocytes exacerbates isoproterenol‑induced cell death and heart failure". International Journal of Molecular Medicine 51, no. 2 (2023): 13. https://doi.org/10.3892/ijmm.2022.5216