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Metabolite Effect on Angiogenesis: Insights from Transcriptome Analysis.

P Sunitha1, Kesavan R Arya1, Achuthsankar S Nair1

  • 1Department of Computational Biology and Bioinformatics, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India.

Cell Biochemistry and Biophysics
|June 14, 2022
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Summary
This summary is machine-generated.

Cellular metabolism, particularly glucose levels, significantly influences angiogenesis by altering genome-wide gene expression. This metabolic dependence is crucial for understanding tumor angiogenesis and developing targeted therapies.

Keywords:
AngiogenesisDifferentially expressed genesEndothelial cellsGlucoseMetaboliteVEGF responsive signature genes

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Metabolic Regulation

Background:

  • Cellular metabolic status impacts endothelial cell angiogenic potential.
  • Previous research linked metabolites like lactate and citrate to VEGFA-VEGFR2 signaling.
  • The effect of metabolic status on genome-wide gene expression in angiogenesis remains unclear.

Purpose of the Study:

  • To investigate how glucose metabolism affects genome-level gene expression in endothelial cells during angiogenesis.
  • To identify key genes and pathways modulated by glucose levels in angiogenesis.

Main Methods:

  • Computational analysis of transcriptome data from human umbilical vein endothelial cells (HUVECs) under varying glucose conditions (in vitro and in vivo).
  • Identification of differentially expressed genes, focusing on the VEGFA-VEGFR2 signaling pathway and VEGF signature genes.

Main Results:

  • Glucose metabolism significantly alters genome-level expression in endothelial cells, impacting angiogenesis.
  • Specific differentially expressed genes within the VEGFA-VEGFR2 pathway and VEGF signature genes were identified as critical hubs.
  • Demonstrated a clear dependence of angiogenesis on metabolite levels, especially glucose.

Conclusions:

  • Angiogenesis is metabolically dependent, with glucose availability playing a key regulatory role at the genomic level.
  • Understanding this glucose-mediated genomic modulation is vital for comprehending tumor angiogenesis.
  • Metabolic reprogramming in cancer cells critically influences angiogenesis, offering therapeutic targets.