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

Yonsei Med J. 2019 Apr;60(4):352-359. doi: 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.

Keywords: CTGF; acute aortic dissection; miR-145; progression.

MeSH terms

  • Animals
  • Aortic Dissection / genetics*
  • Aortic Dissection / metabolism
  • Aortic Dissection / pathology*
  • Apoptosis
  • Case-Control Studies
  • Cell Proliferation / genetics
  • Connective Tissue Growth Factor / genetics*
  • Connective Tissue Growth Factor / metabolism
  • Down-Regulation
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • Rats
  • Transfection

Substances

  • CCN2 protein, human
  • MIRN145 microRNA, human
  • MIRN145 microRNA, rat
  • MicroRNAs
  • Connective Tissue Growth Factor