Targeting epigenetic modifiers to reprogramme macrophages in non-resolving inflammation-driven atherosclerosis

Area of Science:

• Cardiovascular Diseases
• Immunology
• Epigenetics

Background:

• Atherosclerosis (AS) is a chronic inflammatory cardiovascular disease driven by uncontrolled inflammation in arterial walls.
• Macrophage plasticity, including polarization to pro- or anti-inflammatory phenotypes, is central to AS pathogenesis.
• Epigenetic mechanisms are increasingly recognized as key regulators of macrophage plasticity and inflammation.

Purpose of the Study:

• To review current findings on the epigenetic regulation of macrophages in the context of AS.
• To elucidate the role of epigenetic modifiers in controlling macrophage polarization and inflammation in AS.
• To discuss challenges and propose strategies for developing epigenetic-targeted anti-atherosclerosis therapies.

Main Methods:

• Review of up-to-date scientific literature on epigenetics, macrophage biology, and atherosclerosis.
• Analysis of identified epigenetic modifiers (e.g., TET2, DNMT3A, HDACs, JMJD3, KDM4A) and their roles.
• Discussion of epigenetic mechanisms including DNA methylation and histone modifications (acetylation, lactylation).

Main Results:

• Epigenetic modifiers significantly influence macrophage polarization and inflammatory responses in AS.
• These modifiers orchestrate transcriptional reprogramming and metabolic rewiring of macrophages.
• Specific epigenetic alterations are linked to the uncontrolled inflammation characteristic of AS.

Conclusions:

• Epigenetic regulation of macrophage plasticity is crucial for understanding AS onset and progression.
• Epigenetic modifiers represent promising therapeutic targets for anti-atherosclerosis strategies.
• Repolarizing macrophages from pro- to anti-inflammatory phenotypes via epigenetic targeting is a potential therapeutic approach.