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Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy

  • Authors:
    • Ling-Peng Wang
    • Rui-Mei Han
    • Bin Wu
    • Meng-Yao Luo
    • Yun-Hui Deng
    • Wei Wang
    • Chao Huang
    • Xiang Xie
    • Jian Luo
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The First Affiliated Hospital, Xinjihypang Medical University, Urumqi, Xinjiang 830000, P.R. China, Department of Cardiology, Shanghai Xuhui Central Hospital, Shanghai 200031, P.R. China, Department of Geriatrics, Xinjiang Military General Hospital, Urumqi, Xinjiang 830000, P.R. China, Department of Internal Medicine, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 146
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    Published online on: November 9, 2022
       https://doi.org/10.3892/ijmm.2022.5202
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Abstract

The activation of mammalian ste20‑like kinase1 (Mst1) is a crucial event in cardiac disease development. The inhibition of Mst1 has been recently suggested as a potential therapeutic strategy for the treatment of diabetic cardiomyopathy. However, whether silencing Mst1 also protects against hypertensive (HP) myocardial injury, or the mechanisms through which this protection is conferred are not yet fully understood. The present study aimed to explore the role of Mst1 in HP myocardial injury using in vivo and in vitro hypertension (HP) models. Angiotensin II (Ang II) was used to establish HP mouse and cardiac microvascular endothelial cell (CMEC) models. CRISPR/adenovirus vector transfection was used to silence Mst1 in these models. Using echocardiography, hematoxylin and eosin staining, Masson's trichrome staining, the enzyme‑linked immunosorbent assay detection of inflammatory factors, the enzyme immunoassay detection of oxidative stress markers, terminal deoxynucleotidyl transferase dUTP nick‑end labeling staining, scanning electron microscopy, transmission electron microscopy, as well as immunofluorescence and western blot analysis of the autophagy markers, p62, microtubule‑associated proteins 1A/1B light chain 3B and Beclin‑1, it was found that Ang II induced HP myocardial injury with impaired cardiac function, increased the expression of inflammatory factors, and elevated oxidative stress in mice. In addition, it was found that Ang II reduced autophagy, enhanced apoptosis, and disrupted endothelial integrity and mitochondrial membrane potential in cultured CMECs. The silencing of Mst1 in both in vivo and in vitro HP models attenuated the HP myocardial injury. On the whole, these findings suggest that Mst1 is a key contributor to HP myocardial injury through the regulation of cardiomyocyte autophagy.
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Copy and paste a formatted citation
Spandidos Publications style
Wang L, Han R, Wu B, Luo M, Deng Y, Wang W, Huang C, Xie X and Luo J: Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy. Int J Mol Med 50: 146, 2022.
APA
Wang, L., Han, R., Wu, B., Luo, M., Deng, Y., Wang, W. ... Luo, J. (2022). Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy. International Journal of Molecular Medicine, 50, 146. https://doi.org/10.3892/ijmm.2022.5202
MLA
Wang, L., Han, R., Wu, B., Luo, M., Deng, Y., Wang, W., Huang, C., Xie, X., Luo, J."Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy". International Journal of Molecular Medicine 50.6 (2022): 146.
Chicago
Wang, L., Han, R., Wu, B., Luo, M., Deng, Y., Wang, W., Huang, C., Xie, X., Luo, J."Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy". International Journal of Molecular Medicine 50, no. 6 (2022): 146. https://doi.org/10.3892/ijmm.2022.5202
Copy and paste a formatted citation
x
Spandidos Publications style
Wang L, Han R, Wu B, Luo M, Deng Y, Wang W, Huang C, Xie X and Luo J: Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy. Int J Mol Med 50: 146, 2022.
APA
Wang, L., Han, R., Wu, B., Luo, M., Deng, Y., Wang, W. ... Luo, J. (2022). Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy. International Journal of Molecular Medicine, 50, 146. https://doi.org/10.3892/ijmm.2022.5202
MLA
Wang, L., Han, R., Wu, B., Luo, M., Deng, Y., Wang, W., Huang, C., Xie, X., Luo, J."Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy". International Journal of Molecular Medicine 50.6 (2022): 146.
Chicago
Wang, L., Han, R., Wu, B., Luo, M., Deng, Y., Wang, W., Huang, C., Xie, X., Luo, J."Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy". International Journal of Molecular Medicine 50, no. 6 (2022): 146. https://doi.org/10.3892/ijmm.2022.5202
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