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MicroRNA‑217 is involved in the progression of atherosclerosis through regulating inflammatory responses by targeting

Liyun Zhang1, Juan Chen1, Qin He1

  • 1Department of Cardiology, Wuhan Central Hospital, Wuhan, Hubei 430015, P.R. China.

Molecular Medicine Reports
|August 22, 2019
PubMed

Insights

Downregulating microRNA-217 (miR-217) may alleviate atherosclerosis by reducing macrophage apoptosis and inflammation. This occurs through targeting sirtuin 1 (SIRT1), a key factor in the SIRT1/AMPK/NF-κB pathway, offering a potential therapeutic strategy.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Inflammation Research

Background:

  • Atherosclerosis is a global health issue driven by chronic inflammation, necessitating novel therapeutic targets.
  • MicroRNAs (miRNAs) play significant roles in atherosclerosis, but the specific function of miR-217 remains largely unknown.

Purpose of the Study:

  • To investigate the role and underlying mechanism of miR-217 in the pathogenesis of atherosclerosis.
  • To explore miR-217's potential as a therapeutic target for atherosclerosis.

Main Methods:

  • Quantified miR-217 levels in atherosclerosis patients' blood using reverse transcription-quantitative PCR.
  • Established an in vitro macrophage model using THP-1 cells treated with oxidized low-density lipoprotein (ox-LDL).
  • Validated miR-217 targeting of sirtuin 1 (SIRT1) via TargetScan and dual luciferase reporter assays; assessed cell apoptosis, pro-inflammatory factors, and lipid levels.

Main Results:

  • miR-217 was significantly upregulated in atherosclerosis patients.
  • SIRT1 was identified as a direct target of miR-217 and was downregulated in atherosclerosis.
  • Downregulating miR-217 reduced ox-LDL-induced increases in triglyceride, total cholesterol, macrophage apoptosis, and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β).

Conclusions:

  • miR-217 downregulation alleviates atherosclerosis by inhibiting macrophage apoptosis and inflammation via targeting SIRT1.
  • The SIRT1/AMPK/NF-κB pathway is implicated in miR-217's effects on macrophages.
  • Therapeutic strategies targeting miR-217 may offer a novel approach to managing atherosclerosis.

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