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Identification and experimental validation of KMO as a critical immune-associated mitochondrial gene in unstable atherosclerotic plaque

  • 0Department of Cardiovascular Medicine, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, Guizhou, 550004, China.
Journal of Translational Medicine +

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July 18, 2024

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July 18, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Kynurenine 3-monooxygenase (KMO) is identified as a promising biomarker for unstable atherosclerotic plaques. Silencing KMO in mice reduced plaque formation and improved stability, suggesting KMO’s role in cardiovascular events.

Area Of Science

  • Cardiovascular Research
  • Biomarker Discovery
  • Bioinformatics

Background

  • Atherosclerotic plaque instability increases cardiovascular and cerebrovascular event risk.
  • Lack of effective diagnostic biomarkers hinders plaque instability assessment.
  • This study aimed to identify novel biomarkers for plaque instability.

Purpose Of The Study

  • To identify hub genes associated with unstable atherosclerotic plaques using bioinformatics.
  • To investigate the diagnostic potential of identified hub genes.
  • To explore the therapeutic implications of targeting these genes.

Main Methods

  • Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning algorithms.
  • Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) for immune cell infiltration.
  • Gene Set Variation Analysis (GSVA) for pathway analysis.
  • Validation using immunohistochemistry (IHC), RT-qPCR, ELISA, and immunofluorescence.
  • In vivo validation in ApoE-/- mice models.

Main Results

  • Significant alterations in CD8 T cells and M0 macrophages observed in atherosclerosis.
  • Six hub genes identified, with KMO showing a positive correlation with M0 macrophages and negative correlation with CD8 T cells.
  • KMO expression significantly upregulated in unstable plaques and associated with macrophage infiltration.
  • KMO silencing in ApoE-/- mice attenuated plaque formation and enhanced plaque stability.

Conclusions

  • Kynurenine 3-monooxygenase (KMO), a mitochondria-targeted gene, is a potential diagnostic biomarker for atherosclerotic plaque instability.
  • KMO is associated with macrophage cells and plays a role in plaque development and stability.
  • Targeting KMO may offer a novel therapeutic strategy for atherosclerosis.

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