Inhibition of miR-155 attenuates abdominal aortic aneurysm in mice by regulating macrophage-mediated inflammation

Zhidong Zhang1,2, Kai Liang1,2, Gangqiang Zou1,2

  • 1Department of Vascular and Endovascular Surgery, Henan Provincial People's Hospital, NO.7 Weiwu Road, Zhengzhou, Henan 450003. P.R. China.

Bioscience Reports
|February 21, 2018
PubMed

Insights

This study reveals microRNA-155 (miR-155) promotes abdominal aortic aneurysm (AAA) by increasing inflammation. Inhibiting miR-155 significantly reduced AAA development in mouse models, highlighting its therapeutic potential.

Area of Science:

  • Vascular Biology
  • Molecular Medicine
  • Inflammation Research

Background:

  • Abdominal aortic aneurysms (AAA) are characterized by inflammation and extracellular matrix degradation.
  • MicroRNAs (miRNAs) play critical roles in cardiovascular diseases, but their specific role in AAA pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the role of miR-155 in AAA development.
  • To determine if miR-155 regulates macrophage-mediated inflammation in AAA pathology.

Main Methods:

  • Utilized Angiotensin II-infused apolipoprotein E-deficient (ApoE-/-) mice and THP-1 cell models.
  • Assessed miR-155 expression via qRT-PCR.
  • Quantified protein levels (MMP-2, MMP-9, iNOS, MCP-1) using Western blotting and ELISA.
  • Evaluated cellular changes (CD68, elastic collagen, VSMC proliferation/migration) through immunostaining and transwell assays.

Main Results:

  • miR-155 and associated inflammatory cytokines were upregulated in AAA patients and mouse models.
  • miR-155 overexpression exacerbated AAA pathology by increasing MMPs, iNOS, MCP-1, and VSMC activity.
  • Inhibition of miR-155 using antagomirs reduced inflammatory markers and pathological features in mice.

Conclusions:

  • miR-155 is a key mediator in AAA development, primarily by promoting macrophage-driven inflammation.
  • Inhibiting miR-155 presents a promising therapeutic strategy for preventing AAA progression.

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