Yonsei Med J.  2019 Apr;60(4):352-359. 10.3349/ymj.2019.60.4.352.

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

• Li T
• Liu C
• Liu L
• Xia H
• Xiao Y
• Wang X
• Wang Y

• KMID: 2450190
• DOI: http://doi.org/10.3349/ymj.2019.60.4.352

Abstract

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.

Keyword

miR-145; acute aortic dissection; progression; CTGF

MeSH Terms

Animals
Apoptosis
Blotting, Western
Connective Tissue Growth Factor
Humans
Luciferases
MicroRNAs
Muscle, Smooth, Vascular
Rats
Tissue Donors
Connective Tissue Growth Factor
Luciferases
MicroRNAs