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Updated: Jun 19, 2026

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
09:06

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice

Published on: February 20, 2019

Therapeutic targets for atherosclerotic coronary artery disease: druggable genome-wide Mendelian randomization

Wenbin Wang1, Yingxian Sun2, Kejia Chang3

  • 1Department of Cardiology, Shenzhen Third People's Hospital, Shenzhen, Guangdong, China; Department of Cardiology, First Hospital of China Medical University, Shenyang, Liaoning, China.

Atherosclerosis
|June 17, 2026
PubMed

Insights

Elevated levels of CES2 and TGFA proteins are linked to a lower risk of atherosclerotic coronary artery disease (ACAD). This suggests potential new drug targets for preventing ACAD.

Area of Science:

  • Genomics
  • Cardiovascular Medicine
  • Pharmacology

Background:

  • Atherosclerotic coronary artery disease (ACAD) remains a leading cause of mortality despite treatment advances.
  • Identifying novel therapeutic targets is crucial for reducing major adverse cardiovascular events.

Purpose of the Study:

  • To integrate genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover druggable genes for ACAD.
  • To identify potential therapeutic targets and drug repurposing opportunities for ACAD.

Main Methods:

  • Drug-target MR analysis using GWAS, cis-eQTL/cis-pQTL data from blood and coronary artery tissue.
  • Phenome-wide association studies (PheWAS), protein-protein interaction (PPI) networks, and in vivo validation.

Main Results:

  • MR identified 57 blood cis-eQTL, 50 blood cis-pQTL, and 5 coronary artery cis-eQTL druggable genes associated with ACAD.
  • CES2 and TGFA showed consistent protective effects; genetically elevated levels correlated with reduced ACAD risk (p < 0.001).
  • Several drugs targeting CES2 and TGFA were identified, with some showing efficacy in vivo.

Conclusions:

  • Genetically determined higher circulating CES2 and TGFA levels are causally linked to decreased ACAD risk.
  • Modulating CES2 and TGFA presents potential therapeutic avenues for ACAD prevention.
  • Candidate drugs targeting these proteins warrant further investigation for repurposing in ACAD treatment.
Abstract

Keywords:
Atherosclerotic coronary artery diseaseDruggable genesMendelian randomization

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