Regulatory Mechanism of MicroRNA-145 in the Pathogenesis of Acute Aortic Dissection.

YONSEI MEDICAL JOURNAL(2019)

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摘要
Purpose: Previous studies have confirmed that microRNAs play important roles in the pathogenesis of acute aortic dissection (AAD). Here, we aimed to explore the role of miR-145 and its regulatory mechanism in the pathogenesis of AAD. Materials and Methods: AAD tissue samples were harvested from patients with aortic dissection and normal donors. Rat aortic vascular smooth muscle cells (VSMCs) were transfected with miR-145 mimic/inhibitor or negative control mimic/inhibitor. Gene and protein expression was measured in human aortic dissection tissue specimens and VSMCs by qRT-PCR and Western blot. Luciferase reporter assay was applied to verify whether connective tissue growth factor (CTGF) was a direct target of miR-145 in VSMCs. Methyl thiazolyl tetrazolium assay was used to detect VSMC viability. Results: miR-145 expression was downregulated in aortic dissection tissues and was associated with the survival of patients with AAD. Overexpression of miR-145 promoted VSMC proliferation and inhibited cell apoptosis. Moreover, CTGF, which was increased in aortic dissection tissues, was decreased by miR-145 mimic and increased by miR-145 inhibitor. Furthermore, CTGF was confirmed as a target of miR-145 and could reverse the promotion effect of miR-145 on the progression of AAD. Conclusion: miR-145 suppressed the progression of AAD by targeting CTGF, suggesting that a miR-145/CTGF axis may provide a potential therapeutic target for AAD.
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关键词
miR-145,acute aortic dissection,progression,CTGF
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