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Updated: Aug 27, 2025

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Identification of the Transcription Factor ATF3 as a Direct and Indirect Regulator of the LDLR

Sabine Bauer1,2, Jana Eigenmann1, Yuqi Zhao3

  • 1Department of Cardiology, German Heart Centre Munich, Technical University Munich, 80636 Munich, Germany.

Metabolites
|September 23, 2022
PubMed

Insights

Activating transcription factor 3 (ATF3) regulates liver networks impacting cholesterol and inflammation in coronary artery disease (CAD). Targeting ATF3 may offer a novel approach to reduce cardiovascular risk by managing LDL cholesterol.

Area of Science:

  • Molecular biology
  • Cardiovascular research
  • Genetics

Background:

  • Coronary artery disease (CAD) involves complex inflammation and cholesterol metabolism.
  • Tissue-specific signaling pathways in CAD pathogenesis remain under-explored.

Purpose of the Study:

  • Identify key molecular regulators in liver networks relevant to atherosclerosis.
  • Investigate the role of activating transcription factor 3 (ATF3) in cholesterol metabolism and inflammation.

Main Methods:

  • Analysis of liver-specific transcriptomes from human and mouse studies.
  • Chromatin immunoprecipitation DNA sequencing (ChIP-seq) in human liver cells.
  • siRNA knockdown experiments in Hep3B liver cells.
  • Examination of human (STARNET) and mouse (HMDP) liver expression data.

Main Results:

  • ATF3 identified as a key regulator of liver networks linked to atherosclerosis, inflammation, and cholesterol.
  • ATF3 directly and indirectly regulates low-density lipoprotein receptor (LDLR) expression.
  • ATF3 binding motifs found in MAFF and LDLR promoter regions.
  • ATF3 knockdown upregulates LDLR; LPS-induced inflammation upregulates ATF3 and downregulates LDLR.

Conclusions:

  • ATF3 plays a significant role in regulating cholesterol metabolism and inflammation in the liver.
  • ATF3 is a potential therapeutic target for managing LDL cholesterol levels.
  • Targeting ATF3 may reduce cardiovascular risk in patients with coronary artery disease.
Keywords:
ATF3LDLRLPSMAFFatherosclerosiscardiovascular diseasecoronary artery diseasegene expressioninflammationlipid metabolismliver metabolismtranscription factor

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