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


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.

SUBMITTER: Sun Y 

PROVIDER: S-EPMC6831472 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Sun Yudong Y   Xiao Yu Y   Sun Huiying H   Zhao Zhiqing Z   Zhu Jiang J   Zhang Lei L   Dong Jian J   Han Tonglei T   Jing Qing Q   Zhou Jian J   Jing Zaiping Z  

Theranostics 20191018 25


<b>Rationale:</b> 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. <b>Methods:</b> We harvested aortas from normal and AD patients to expl  ...[more]

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