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Epigenetic modulators mitigate angiogenesis through a complex transcriptomic network.

T V Shiva Shankar1, L Willems1

  • 1Molecular and Cellular Epigenetics (GIGA-Cancer) and Molecular Biology (GxABT), University of Liège (ULg), Liège, Belgium.

Vascular Pharmacology
|January 22, 2014
PubMed
Summary
This summary is machine-generated.

Epigenetic mechanisms like lysine acetylation and cytosine methylation regulate genes involved in blood vessel formation (angiogenesis). Inhibitors targeting these epigenetic modifications offer a promising, multitargeted therapeutic strategy for diseases with excessive angiogenesis.

Keywords:
5-Aza-2′-deoxycytidine (PubChem CID: 451668)AngiogenesisCytosine methylationLysine acetylationNVP-LAQ824 (PubChem CID: 6445533)Romidepsin (PubChem CID: 5352062)Scriptaid (PubChem CID: 5186)Suberoylanilide hydroxamic acid (PubChem CID: 5311)Trichostatin A (PubChem CID: 444732)Valproic acid (PubChem CID: 3121)Zebularine (PubChem CID: 100016)

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Angiogenesis, the formation of new blood vessels, is a critical process in development and disease.
  • Epigenetic modifications, including DNA methylation and histone modifications, play a crucial role in gene expression regulation.
  • Dysregulated angiogenesis is implicated in various pathologies, including cancer and ischemic diseases.

Purpose of the Study:

  • To review the current understanding of epigenetic regulation in angiogenesis.
  • To highlight the specific roles of lysine acetylation and cytosine methylation in controlling angiogenic gene expression in endothelial cells.
  • To explore the therapeutic potential of epigenetic inhibitors in managing angiogenesis-related disorders.

Main Methods:

  • Review of existing literature on epigenetics and angiogenesis.
  • Analysis of transcriptomic data to identify genes regulated by epigenetic modulators.
  • Examination of the effects of lysine acetylation and cytosine methylation inhibitors on angiogenic gene expression.

Main Results:

  • Lysine acetylation and cytosine methylation are identified as key transcriptional regulators of angiogenic genes in endothelial cells.
  • Epigenetic inhibitors modulate the transcriptome, impacting the expression of critical angiogenic factors like VEGF and eNOS.
  • Transcriptomic profiling revealed novel genes affected by these epigenetic modulators.

Conclusions:

  • Epigenetic mechanisms provide a significant layer of control over angiogenesis.
  • The reversibility and tolerability of epigenetic inhibitors suggest their potential as therapeutic agents for pathological angiogenesis.
  • A multitargeted epigenetic approach may overcome resistance mechanisms associated with single-target anti-angiogenic therapies.