MicroRNA-23a-5p promotes atherosclerotic plaque progression and vulnerability by repressing ATP-binding cassette

Shuai Yang1, Zi-Ming Ye2, Shengcai Chen1

  • 1Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Insights

MicroRNA-23a-5p (miR-23a-5p) promotes vulnerable plaque formation in atherosclerosis by inhibiting cholesterol efflux. Inhibiting miR-23a-5p offers a potential therapeutic strategy to stabilize plaques and prevent stroke.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Biochemistry

Background:

  • Vulnerable atherosclerotic plaques in carotid arteries are a primary cause of acute ischemic stroke (AIS).
  • Early detection and intervention for vulnerable plaques remain challenging.
  • MicroRNAs (miRNAs) play critical roles in regulating cellular processes relevant to atherosclerosis.

Purpose of the Study:

  • To investigate the role of specific miRNAs in the development and progression of vulnerable atherosclerotic plaques.
  • To identify novel molecular targets and therapeutic strategies for atherosclerosis and AIS.

Main Methods:

  • Microarray analysis of plasma miRNAs in AIS patients with vulnerable plaques.
  • Expression analysis of miR-23a-5p in plasma and macrophages from atherosclerosis mouse models.
  • Bioinformatics analysis and in vitro experiments to identify miR-23a-5p targets.
  • Luciferase reporter assays to confirm miR-23a-5p binding to target 3' UTRs.
  • In vitro functional assays assessing cholesterol efflux and foam cell formation.
  • In vivo studies using ApoE-/- mice treated with miR-23a-5p antagomir.

Main Results:

  • miR-23a-5p was significantly elevated in AIS patients with vulnerable plaques and correlated with plaque progression.
  • miR-23a-5p expression was increased in plasma and macrophages of atherosclerosis mice.
  • ATP-binding cassette transporters A1/G1 (ABCA1/G1) were identified as novel targets of miR-23a-5p.
  • miR-23a-5p inhibition enhanced cholesterol efflux and reduced foam cell formation by upregulating ABCA1/G1.
  • Systemic delivery of miR-23a-5p antagomir increased ABCA1/G1 expression, reduced atherosclerosis, and promoted plaque stability in vivo.

Conclusions:

  • miR-23a-5p is a key regulator in the progression and vulnerability of atherosclerotic plaques.
  • miR-23a-5p promotes macrophage-derived foam cell formation.
  • Targeting miR-23a-5p with antagomirs represents a promising therapeutic approach for atherosclerosis and stroke prevention.

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