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Circ_0004104 knockdown alleviates oxidized low-density lipoprotein-induced dysfunction in vascular endothelial cells

Chi Zhang1, Liyue Wang1, Ying Shen2

  • 1Department of Cardiology, The Puren Hospital, No. 218, Changqing First Road, Jianghan District, Wuhan, 430081, Hubei, China.

BMC Cardiovascular Disorders
|April 24, 2021
PubMed

Insights

Circular RNA circ_0004104 exacerbates atherosclerosis by upregulating TRIM14 via sponging miR-328-3p in endothelial cells. Knockdown of circ_0004104 protects against oxidized low-density lipoprotein-induced cellular dysfunction.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Cell Biology

Background:

  • Circular RNAs (circRNAs) play crucial roles in cardiovascular diseases, including atherosclerosis (AS).
  • The specific role of circ_0004104 in AS remains largely unexplored.
  • This study investigates the function and mechanism of circ_0004104 in AS pathogenesis.

Purpose of the Study:

  • To elucidate the role of circ_0004104 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell dysfunction.
  • To identify the molecular mechanism underlying circ_0004104's function in AS.
  • To explore the potential therapeutic target of circ_0004104 in AS.

Main Methods:

  • Utilized oxidized low-density lipoprotein (ox-LDL) to induce dysfunction in human umbilical vein endothelial cells (HUVECs).
  • Assessed cell viability, apoptosis, angiogenesis, inflammation, and oxidative stress using MTT assays, flow cytometry, capillary-like network formation, and ELISA.
  • Employed dual-luciferase reporter, RNA immunoprecipitation, and RNA-pull down assays to confirm molecular interactions.

Main Results:

  • Ox-LDL exposure upregulated circ_0004104 and promoted HUVEC dysfunction, including reduced viability and angiogenesis, and increased apoptosis, inflammation, and oxidative stress.
  • Circ_0004104 directly targeted microRNA-328-3p (miR-328-3p).
  • Circ_0004104 positively regulated tripartite motif 14 (TRIM14) expression by sponging miR-328-3p, and TRIM14 overexpression reversed miR-328-3p-induced effects.

Conclusions:

  • Circ_0004104 knockdown attenuated ox-LDL-induced HUVEC dysfunction.
  • The protective effect was mediated by the circ_0004104/miR-328-3p/TRIM14 axis.
  • Circ_0004104 represents a potential therapeutic target for atherosclerosis.
Abstract

Keywords:
AtherosclerosisCirc_0004104MiR-328-3pOxidized low-density lipoproteinTRIM14

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