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LncRNA H19 drives atherosclerosis progression via the miR-let-7a/ITGB3 axis

Zi-Yang Hu1, Yuan Li2,3, Long-Yu Liu4

  • 1Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, Guangdong, China.

Insights

Long non-coding RNA H19 promotes atherosclerosis by sponging miR-let-7a, leading to increased ITGB3 and leukocyte recruitment. Inhibiting H19 reduces atherosclerotic lesions, suggesting H19 as a therapeutic target for this inflammatory disease.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Immunology

Background:

  • Atherosclerosis (AS) is a major cause of death driven by chronic inflammation.
  • The role of long non-coding RNA (lncRNA) H19 in AS pathogenesis is not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying H19's role in atherosclerosis.
  • To investigate H19 as a potential therapeutic target for AS.

Main Methods:

  • Established AS mouse and cell models using ApoE-/- mice and HUVECs stimulated with oxLDL.
  • Utilized H19 siRNA and adeno-associated virus (AAV)-sh-H19 to assess H19's functional impact.
  • Performed luciferase reporter assays to confirm direct targeting of miR-let-7a by H19.

Main Results:

  • H19 expression was significantly upregulated in AS models, correlating with increased adhesion molecules and cytokines.
  • H19 acted as a molecular sponge for miR-let-7a, upregulating ITGB3 and promoting leukocyte recruitment.
  • H19 knockdown inhibited endothelial cell adhesion and inflammation, and AAV-sh-H19 treatment reduced AS lesion formation.

Conclusions:

  • The H19/miR-let-7a/ITGB3 axis is a critical inflammatory pathway in AS.
  • Targeting H19 offers a potential therapeutic strategy for preventing atherosclerosis initiation and progression.
Abstract

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