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CHOP Increases TRIB3-Dependent miR-208 Expression to Potentiate Vascular Smooth Muscle Cell Proliferation and

Rui Chen1, Yan Zhang2, Chunyan Zhao3

  • 1Department of Physiology, College of Basic Medical Sciences, Jilin University, No. 126, Xinmin Street, Changchun, 130021, Jilin Province, People's Republic of China.

Cardiovascular Drugs and Therapy
|April 15, 2021
PubMed
Abstract

Insights

Inhibition of C/EBP homologous protein (CHOP) combats atherosclerosis by regulating the TRIB3/miR-208/TIMP3 axis. This mechanism impacts vascular smooth muscle cell proliferation and migration, offering a potential therapeutic strategy.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Atherosclerosis Research

Background:

  • C/EBP homologous protein (CHOP) is a potential therapeutic target for atherosclerosis.
  • The precise mechanism by which CHOP influences atherosclerosis requires further elucidation.

Purpose of the Study:

  • To define the role of CHOP in atherosclerosis.
  • To investigate the underlying molecular mechanism involving the TRIB3/miR-208/TIMP3 axis.

Main Methods:

  • Atherosclerosis mouse models (ApoE-/-) were established using high-fat diets.
  • Loss- and gain-function assays were performed on vascular smooth muscle cells (VSMCs).
  • Key molecular targets including miR-208, TRIB3, and TIMP3 were analyzed, alongside VSMC proliferation, migration, and plaque stability markers.

Main Results:

  • miR-208 expression was elevated in atherosclerotic samples and promoted VSMC proliferation and migration.
  • miR-208 directly targeted TIMP3, and its effects were abrogated by TIMP3 upregulation.
  • CHOP was found to increase TRIB3, subsequently upregulating miR-208 and downregulating TIMP3, thereby enhancing VSMC proliferation and migration.

Conclusions:

  • CHOP inhibition may reduce VSMC proliferation and migration.
  • Targeting the TRIB3/miR-208/TIMP3 axis by inhibiting CHOP could ameliorate atherosclerosis progression.
  • This pathway influences lipid profiles, potentially increasing HDL-C and decreasing TC, TG, and LDL-C.
Keywords:
AtherosclerosisCHOPMicroRNA-208TIMP3TRIB3Vascular smooth muscle cells

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