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miR-3529-3p/ABCA1 axis regulates smooth muscle cell homeostasis by enhancing inflammation via JAK2/STAT3 pathway

Tingyu Wang1, You Yu1, Yinglong Ding1

  • 1Department of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University & Institute for Cardiovascular Science, Soochow University, Suzhou, China.

Frontiers in Cardiovascular Medicine
|September 11, 2024
PubMed
Abstract

Insights

MicroRNA-3529 (miR-3529) is elevated in thoracic aortic dissection (TAD) and disrupts smooth muscle cell homeostasis by altering metabolism via the JAK2/STAT3 pathway. This suggests miR-3529 as a potential therapeutic target for TAD.

Area of Science:

  • Vascular Biology
  • Molecular Medicine
  • Genomics

Background:

  • Thoracic Aortic Dissection (TAD) is a critical condition lacking effective drug therapies.
  • Homeostasis disruption in human aortic smooth muscle cells (HASMCs) is a key pathological feature of TAD.
  • Aberrantly expressed microRNAs (miRNAs) are implicated in TAD pathogenesis and HASMC regulation.

Purpose of the Study:

  • To identify specific miRNAs and their mechanisms contributing to HASMC homeostasis disruption in TAD.
  • To investigate the role of the identified key miRNA, miR-3529, in regulating HASMC function and metabolism.

Main Methods:

  • Utilized bulk miRNA sequencing and qRT-PCR to profile differentially expressed miRNAs in TAD.
  • Employed lentivirus-mediated overexpression of miR-3529 in HASMCs.
  • Conducted integrative transcriptomics and metabolomics analyses to elucidate functional roles.
  • Verified miR-3529 targets using bioinformatics and dual-luciferase reporter assays.

Main Results:

  • miR-3529 was found to be significantly elevated in TAD tissues and confirmed via qRT-PCR.
  • Upregulation of miR-3529 disrupted HASMC homeostasis, reducing contractile markers and increasing pro-inflammatory cytokines.
  • Integrative analyses revealed miR-3529 overexpression altered HASMC metabolism, particularly lipid metabolism.
  • Identified ABCA1 as a direct target of miR-3529, with the miR-3529/ABCA1 axis disrupting HASMC homeostasis via the JAK2/STAT3 pathway.

Conclusions:

  • miR-3529 is elevated in TAD patients and disrupts HASMC homeostasis by reprogramming cellular metabolism through the JAK2/STAT3 signaling pathway.
  • These findings highlight miR-3529 as a novel therapeutic target for treating Thoracic Aortic Dissection.
Keywords:
ABCA1homeostasismiR-3529-3psmooth muscle cellthoracic aortic dissection

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