Open Access

Understanding the molecular role of syndecan‑1 in the regulation of caspase‑6 during the progression of cardiac arrhythmia

  • Authors:
    • Yuanchu Wu
    • Lin Chen
    • Caihong Wang
  • View Affiliations

  • Published online on: August 16, 2021     https://doi.org/10.3892/etm.2021.10614
  • Article Number: 1180
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The role of caspase‑6 in heart disease is not well understood, particularly with respect to cardiac arrhythmia. Also, the function of syndecan‑1 in the stimulation of inflammation or a regenerative response after cardiac injury is unclear. Leptin receptor‑deficient (C57BL/KS‑leprdb/leprdb) mice were used in the present study. In addition to developing type 2 diabetes, they also develop initial‑ and end‑stage cardiac arrhythmia after 5 and 8 months, respectively. The initial and end‑stage arrhythmias were confirmed through progressive variations in the PP intervals observable in electrocardiograms. Histopathological images of the cardiac tissue exhibited scattered and loosened cardiac cells at the initial stage of cardiac arrhythmia, whereas tissue hardness and extensive structural changes in cardiomyocytes were evident at the end stage. At the molecular level, the progressive upregulation of caspase‑6 was observed as the cardiac arrhythmia progressed. In the initial stage of arrhythmia, immunohistochemistry revealed that caspase‑6 was expressed at the surface of cardiac cells, suggesting that caspase‑6 targeted the extracellular matrix, leading to a loosening of the cardiac tissue structure. In the end stage of cardiac arrhythmia, caspase‑6 expression was abundant in the cytoplasm, as well as at the cell surface, suggesting that caspase‑6 may have cleaved intermediate filaments, paving the way for cellular morphological changes and apoptosis. Notably, syndecan‑1 was upregulated 5.8‑fold in the initial stage of cardiac arrhythmia, but downregulated at the end stage. Syndecan‑1 may restrict the expression of caspase‑6 in the initial stage of cardiac arrhythmia, while its downregulation at the end stage may allow destructive changes via caspase‑6 overexpression. Furthermore, the knockdown of syndecan‑1 using small interfering RNA enhanced the expression of caspase‑6 in the cardiac tissue by factors of 1.8 and 1.2 at the initial and end stages of cardiac arrhythmia, respectively, compared with that in non‑silenced cardiac tissue. Therefore, it may be concluded that syndecan‑1 plays a major role in the regulation of caspase‑6 during the pathological stages of cardiac arrhythmia.
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October-2021
Volume 22 Issue 4

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Spandidos Publications style
Wu Y, Chen L and Wang C: Understanding the molecular role of syndecan‑1 in the regulation of caspase‑6 during the progression of cardiac arrhythmia. Exp Ther Med 22: 1180, 2021
APA
Wu, Y., Chen, L., & Wang, C. (2021). Understanding the molecular role of syndecan‑1 in the regulation of caspase‑6 during the progression of cardiac arrhythmia. Experimental and Therapeutic Medicine, 22, 1180. https://doi.org/10.3892/etm.2021.10614
MLA
Wu, Y., Chen, L., Wang, C."Understanding the molecular role of syndecan‑1 in the regulation of caspase‑6 during the progression of cardiac arrhythmia". Experimental and Therapeutic Medicine 22.4 (2021): 1180.
Chicago
Wu, Y., Chen, L., Wang, C."Understanding the molecular role of syndecan‑1 in the regulation of caspase‑6 during the progression of cardiac arrhythmia". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1180. https://doi.org/10.3892/etm.2021.10614