Targeting epigenetics as atherosclerosis treatment: an updated view

Area of Science:

• Cardiovascular Research
• Epigenetics
• Pharmacology

Background:

• Atherosclerosis is a significant cause of cardiovascular disease (CVD).
• Epigenetic modifications play a role in the development and progression of atherosclerosis.
• Novel therapeutic strategies targeting epigenetic mechanisms are under investigation for CVD.

Purpose of the Study:

• To review current developments in epigenetic inhibition for atherosclerosis treatment.
• To evaluate the potential of targeting epigenetic factors like histone deacetylates (HDACs) and bromodomain and extraterminal domain (BET) proteins.

Main Methods:

• Review of preclinical and clinical studies on epigenetic inhibitors in atherosclerosis.
• Analysis of the BETonMACE Phase III clinical trial data for apabetalone (RVX-208).

Main Results:

• Preclinical and early clinical studies showed encouraging results for epigenetic modulation in atherosclerosis.
• The BETonMACE trial, targeting BET proteins, did not show a significant effect on major adverse cardiovascular events (MACE) in the studied high-risk population.
• Subgroup analyses and study power considerations suggest potential for apabetalone in specific patient profiles.

Conclusions:

• Epigenetic inhibition represents a promising therapeutic avenue for atherosclerosis and CVD.
• Despite mixed results from the first Phase III BET inhibitor trial, further investigation and development of epigenetic therapies are warranted.
• Targeting repressive histone modifications offers a future direction for atherosclerosis treatment.