miR-27a regulates vascular remodeling by targeting endothelial cells' apoptosis and interaction with vascular smooth muscle cells in aortic dissection

Sun, Yudong; Xiao, Yu; Sun, Huiying; Zhao, Zhiqing; Zhu, Jiang; Zhang, Lei; Dong, Jian; Han, Tonglei; Jing, Qing; Zhou, Jian; Jing, Zaiping

doi:10.7150/thno.35737

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Nanotheranostics 2024; 8(3): 380-400. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(3): 344-379. [Abstract] [Full text] [PDF] [PubMed] [PMC]

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Theranostics 2019; 9(25):7961-7975. doi:10.7150/thno.35737 This issue Cite

Research Paper

miR-27a regulates vascular remodeling by targeting endothelial cells' apoptosis and interaction with vascular smooth muscle cells in aortic dissection

Yudong Sun^1,2*, Yu Xiao^1*, Huiying Sun¹, Zhiqing Zhao¹, Jiang Zhu¹, Lei Zhang¹, Jian Dong¹, Tonglei Han¹, Qing Jing³, Jian Zhou¹, Zaiping Jing^1✉

1. Department of vascular surgery, Changhai Hospital, The Naval Military Medical University, Shanghai, China.
2. Depaertment of general surgery, Jingling Hospital, Medical School of Nanjing University, Nanjing, China
3. Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
^*These authors contributed equally to the study

Citation:

Sun Y, Xiao Y, Sun H, Zhao Z, Zhu J, Zhang L, Dong J, Han T, Jing Q, Zhou J, Jing Z. miR-27a regulates vascular remodeling by targeting endothelial cells' apoptosis and interaction with vascular smooth muscle cells in aortic dissection. Theranostics 2019; 9(25):7961-7975. doi:10.7150/thno.35737. https://www.thno.org/v09p7961.htm

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Abstract

Rationale: Aortic dissection (AD) is caused by functional disorder of cells in the aortic wall, which is largely attributed to vascular remodeling. Therapeutic strategies for AD remain limited due to our incomplete understanding of the role of endothelial cells (ECs) in AD pathogenesis. This study aimed to identify the regulatory role of miR-27a in AD and provide a mechanistic basis for a non-invasive treatment of AD.

Methods: We harvested aortas from normal and AD patients to explore the expression of miR-27a. In vitro and in vivo assays were preformed to explore the biological effects of differential expression of miR-27a in ECs and its regulatory effect on AD.

Results: MiR-27a was lower in intima of AD samples than in healthy individuals. Downregulation of miR-27a in EC was due to up-regulated expression of fas-associated protein with death domain (FADD) and the activation of apoptosis pathway, which led to apoptosis of ECs. Migration of vascular smooth muscle cells was promoted by EC after downregulation of miR-27a due to enhancement of growth/differentiation factor 8 (GDF8) and repression of matrix metalloproteinase-20 (MMP20) in the co-culture system supernatants. Increase in FADD and apoptosis of ECs to induce AD was shown using mouse models of AD in which miR-27a was stably knocked-down by antagomir. Up-regulation of miR-27a by agomir led to a protective effect on AD.

Conclusion: Treatment with miR-27a activator that targets apoptosis of ECs strongly diminished occurrence of AD, providing a new strategy for this disease.

Keywords: aortic dissection, miR-27a, endothelial cell, apoptosis, FADD

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APA

Sun, Y., Xiao, Y., Sun, H., Zhao, Z., Zhu, J., Zhang, L., Dong, J., Han, T., Jing, Q., Zhou, J., Jing, Z. (2019). miR-27a regulates vascular remodeling by targeting endothelial cells' apoptosis and interaction with vascular smooth muscle cells in aortic dissection. Theranostics, 9(25), 7961-7975. https://doi.org/10.7150/thno.35737.

ACS

Sun, Y.; Xiao, Y.; Sun, H.; Zhao, Z.; Zhu, J.; Zhang, L.; Dong, J.; Han, T.; Jing, Q.; Zhou, J.; Jing, Z. miR-27a regulates vascular remodeling by targeting endothelial cells' apoptosis and interaction with vascular smooth muscle cells in aortic dissection. Theranostics 2019, 9 (25), 7961-7975. DOI: 10.7150/thno.35737.

NLM

CSE

Sun Y, Xiao Y, Sun H, Zhao Z, Zhu J, Zhang L, Dong J, Han T, Jing Q, Zhou J, Jing Z. 2019. miR-27a regulates vascular remodeling by targeting endothelial cells' apoptosis and interaction with vascular smooth muscle cells in aortic dissection. Theranostics. 9(25):7961-7975.

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