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XAV939 Improves the Prognosis of Myocardial Infarction by Blocking the Wnt/β-Catenin Signalling Pathway

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Abstract

Myocardial infarction (MI) is closely related to the Wnt signalling pathway, but the role of XAV939 (a Wnt/β-catenin signalling pathway blocker) in MI has not been elucidated. The purpose of this study was to explore the role of XAV939 in mouse hearts and to provide a new and feasible treatment for improving the prognosis of MI. C57BL/6 (male, 8 weeks old, 20–25 g) mice were selected for our study. The MI model was made by ligating the left anterior descending coronary artery. On day 28 after the operation, cardiac function was examined by echocardiography. Infarct size, fibrosis, and angiogenesis were individually measured by TTC assays, Masson’s trichrome staining, and CD31 analysis, respectively. Apoptosis was examined by TdT-mediated dUTP nick-end labelling (TUNEL) staining. The expression of Wnt, β-catenin, caspase 3, Bax, and Bcl-2 was determined by western blotting. XAV939 successfully blocked Wnt/β-catenin signalling pathway activation in cardiomyocytes after MI by promoting the degradation of β-catenin. XAV939 suppressed fibrosis and apoptosis, promoted angiogenesis, reduced myocardial infarct size and improved cardiac function after MI. XAV939 can reduce myocardial infarct size and improve cardiac function by blocking the Wnt/β-catenin signalling pathway, which may provide a new strategy for improving the prognosis of MI.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This research was supported by grants from the key project of Jiangsu Vocational College of Medicine (no. 20229JH02) and the General Project of Natural Science Foundation in Hainan Province, China (no. 821MS0851).

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Authors and Affiliations

  1. Department of Cardiology, Jianhu Clinical College, Jiangsu Vocational College of Medicine, 224700, Yancheng, China

    Zhu Zhang, Jiancheng Qi & Xiucai Fan

  2. Department of Cardiology, West China (Sanya) Hospital, Sichuan University, No. 228 Jiefang Road, Sanya, 572022, Hainan, China

    Min Pan

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  1. Zhu Zhang
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Contributions

Min Pan conceived the study and designed experiments. Zhu Zhang drafted the manuscript and performed the experiments. Jiancheng Qi and Xiucai Fan collected and analyzed data. Min Pan and Zhu Zhang confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.

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Correspondence to Min Pan.

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All procedures were in accordance with the regulations of the Ethics Committee of Laboratory Animal Centre of Nantong University and were performed in accordance with the Guide for the Declaration of Helsinki.

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Zhang, Z., Qi, J., Fan, X. et al. XAV939 Improves the Prognosis of Myocardial Infarction by Blocking the Wnt/β-Catenin Signalling Pathway. Appl Biochem Biotechnol 196, 605–615 (2024). https://doi.org/10.1007/s12010-023-04485-y

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