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Calcium-sensing receptor-mediated mitogen-activated protein kinase pathway improves the status of transplanted mouse embryonic stem cells in rats with acute myocardial infarction

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Abstract

Several studies have identified the critical role of calcium-sensing receptors (CaSRs) in cardiac ischaemia/reperfusion injury and cardiac hypertrophy and have demonstrated that CaSRs induce myocardial apoptosis by activating MAPKs. Using acute myocardial infarction rat models, we found that a combination therapy of CaSR inhibition and embryonic stem cell (ESC) transplantation after acute myocardial infarction (AMI) leads to a dramatic reduction in the infarct size; a significant increase in the maximum rising and falling rate (+dp/dtmax and −dp/dtmax, respectively) of left ventricular pressure; a significant decrease in left ventricular end-diastolic pressure; a significant decrease in the mRNA expression level of CaSR, Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, p-ERK, p-JNK and p-P38 protein together with apoptosis indexes in the C and E groups; and a significant decrease in cTnT levels as well as LDH and CK activity. These findings indicate that cardiac function could be enhanced significantly by combination therapy with CaSR inhibition and ESC transplantation; the effect was better than ESC transplantation alone, and the mechanism might be associated with a reduction in cell apoptosis via the inhibition of the MAPK pathway. Apoptosis could be reduced through CaSR, which regulates the MAPK pathway and apoptosis-related protein. Our study indicated that CaSR inhibitors have a pivotal role in the treatment of AMI.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81300163, 81200160).

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Authors and Affiliations

  1. Mudanjiang Medical University, Mudanjiang, China

    Jian Sun, Tao Wei, Hongtao Zhao, Xiaoqin Liu, Jinfeng Yu, Li Li, Gaochen Song & Hairong Luan

  2. Department of Pathophysiology, Harbin Medical University, Harbin, China

    Shuzhi Bai & Changqing Xu

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  1. Jian Sun
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  2. Tao Wei
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  3. Shuzhi Bai
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  4. Hongtao Zhao
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  5. Xiaoqin Liu
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  7. Li Li
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  8. Gaochen Song
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  9. Hairong Luan
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  10. Changqing Xu
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Correspondence to Jian Sun.

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Sun, J., Wei, T., Bai, S. et al. Calcium-sensing receptor-mediated mitogen-activated protein kinase pathway improves the status of transplanted mouse embryonic stem cells in rats with acute myocardial infarction. Mol Cell Biochem 431, 151–160 (2017). https://doi.org/10.1007/s11010-017-2987-z

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  • DOI: https://doi.org/10.1007/s11010-017-2987-z

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