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The relevance of epigenetics to occlusive cerebral and peripheral arterial disease

Smriti Murali Krishna1, Alexandra Fay Trollope1, Jonathan Golledge1

  • 1*Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia.

Clinical Science (London, England : 1979)
|February 12, 2015
PubMed

Insights

Epigenetic changes, like DNA hypermethylation, are involved in artery disease. However, challenges remain in developing rapid, safe epigenetic therapies for conditions like stroke and limb loss.

Area of Science:

  • Cardiovascular Science
  • Epigenetics
  • Vascular Biology

Background:

  • Athero-thrombosis of brain and limb arteries causes stroke and limb loss.
  • Epigenetic modifications, including DNA hypermethylation and histone alterations, are increasingly implicated in atherosclerosis and ischemic injury.
  • Oxidized low-density lipoprotein-regulated inflammation in endothelial cells involves histone modifications.

Purpose of the Study:

  • To review the role of epigenetics in athero-thrombosis and ischemic injury.
  • To identify challenges in translating epigenetic findings into clinical therapies for athero-thrombosis.

Main Methods:

  • Literature review of epigenetic mechanisms in atherosclerosis.
  • Analysis of challenges in clinical translation of epigenetic therapies.
  • Evaluation of pre-clinical data on epigenetic drugs for ischemic injury.

Main Results:

  • Epigenetic changes, such as DNA hypermethylation and histone modifications (e.g., H3 phosphorylation/acetylation, H4 acetylation), are linked to athero-thrombosis and inflammation.
  • Significant challenges exist in developing epigenetic therapies due to narrow therapeutic windows and safety concerns in co-morbid patients.
  • Pre-clinical studies show conflicting results for novel epigenetic drugs, indicating a need for further research.

Conclusions:

  • Epigenetics plays a crucial role in the development and progression of athero-thrombosis and ischemic injury.
  • Overcoming challenges related to therapeutic window, safety, and efficacy is essential for clinical application of epigenetic therapies.
  • Further in-depth research is required to validate epigenetic drugs before they can be used in clinical practice for athero-thrombosis.

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