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Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection

  • Authors:
    • Shishan Xue
    • Shuai Leng
    • Fengquan Zhang
    • Zhiqiao Dang
    • Guohai Su
    • Wenqian Yu
  • View Affiliations / Copyright

    Affiliations: Department of Cardiac Surgery, Research Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, P.R. China
    Copyright: © Xue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 145
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    Published online on: February 19, 2024
       https://doi.org/10.3892/etm.2024.12433
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Abstract

Thoracic aortic aneurysms (TAAs) are a major cause of death owing to weaker blood vessel walls and higher rupture rates in affected individuals. Vascular smooth muscle cells (VSMCs) are the predominant cell type within the aortic wall and their dysregulation may contribute to TAA progression. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, is involved in several pathological processes; however, the biological functions and mechanisms underlying VSMC phenotype transition and vascular intimal hyperplasia remain unclear. The present study aimed to determine the involvement of EZH2 in mediating VSMC function in the development of TAAs. The expression of EZH2 was revealed to be elevated in patients with thoracic aortic dissection and TAA mouse model through western blotting and reverse transcription‑quantitative PCR experiments. Subsequently, a mouse model was established using β‑aminopropionitrile. In vitro, EdU labeling, Transwell assay, wound healing assay and hematoxylin‑eosin staining revealed that knocking down the Ezh2 gene could reduce the proliferation, invasion, migration, and calcification of mouse primary aortic smooth muscle cells. Flow cytometry analysis found that EZH2 deficiency increased cell apoptosis. Depletion of Ezh2 in mouse primary aortic VSMCs promoted the transformation of VSMCs from a synthetic to a contractile phenotype. Using RNA‑sequencing analysis, it was demonstrated that Ezh2 regulated a group of genes, including integrin β3 (Itgb3), which are critically involved in the extracellular matrix signaling pathway. qChIP found Ezh2 occupies the Itgb3 promoter, thereby suppressing the expression of Itgb3. Ezh2 promotes the invasion and calcification of VSMCs, and this promoting effect is partially reversed by co‑knocking down Itgb3. In conclusion, the present study identified a previously unrecognized EZH2‑ITGB3 regulatory axis and thus provides novel mechanistic insights into the pathophysiological function of EZH2. EZH2 may thus serve as a potential target for the management of TAAs.
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Copy and paste a formatted citation
Spandidos Publications style
Xue S, Leng S, Zhang F, Dang Z, Su G and Yu W: Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection. Exp Ther Med 27: 145, 2024.
APA
Xue, S., Leng, S., Zhang, F., Dang, Z., Su, G., & Yu, W. (2024). Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection. Experimental and Therapeutic Medicine, 27, 145. https://doi.org/10.3892/etm.2024.12433
MLA
Xue, S., Leng, S., Zhang, F., Dang, Z., Su, G., Yu, W."Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection". Experimental and Therapeutic Medicine 27.4 (2024): 145.
Chicago
Xue, S., Leng, S., Zhang, F., Dang, Z., Su, G., Yu, W."Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection". Experimental and Therapeutic Medicine 27, no. 4 (2024): 145. https://doi.org/10.3892/etm.2024.12433
Copy and paste a formatted citation
x
Spandidos Publications style
Xue S, Leng S, Zhang F, Dang Z, Su G and Yu W: Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection. Exp Ther Med 27: 145, 2024.
APA
Xue, S., Leng, S., Zhang, F., Dang, Z., Su, G., & Yu, W. (2024). Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection. Experimental and Therapeutic Medicine, 27, 145. https://doi.org/10.3892/etm.2024.12433
MLA
Xue, S., Leng, S., Zhang, F., Dang, Z., Su, G., Yu, W."Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection". Experimental and Therapeutic Medicine 27.4 (2024): 145.
Chicago
Xue, S., Leng, S., Zhang, F., Dang, Z., Su, G., Yu, W."Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection". Experimental and Therapeutic Medicine 27, no. 4 (2024): 145. https://doi.org/10.3892/etm.2024.12433
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