Objective:

To synthesize recent evidence on the roles of key regulatory proteins in atherogenesis and their potential as therapeutic targets.

Approach:

• Epigenetic Modifiers: Examines the role of histone deacetylases, Sirtuins, EZH2, and TET2 in chromatin remodeling and pro-inflammatory gene activation.
• Transcription Factors: Describes how KLFs, PPARs, Nrf2, and BACH1 link metabolic homeostasis with anti-inflammatory responses.
• Membrane Signaling Axes: Details the impact of Eph receptors, Notch, and the SIRPα-CD47 checkpoint on endothelial dysfunction and macrophage polarization.
• Cellular Metabolism: Discusses the roles of UCP and ANGPTL proteins in regulating cellular metabolism and inflammasome activity.

Key Findings:

• HDACs exhibit isoform-specific effects on atherosclerosis, with HDAC3 and HDAC9 playing significant roles in inflammation and endothelial dysfunction.
• Transcription factors coordinate vascular anti-inflammatory defenses and metabolic homeostasis.
• Membrane-associated signaling pathways modulate intercellular communication and plaque stability.

Interpretation:

Understanding the complex interactions among epigenetic, transcriptional, and signaling pathways is crucial for developing targeted therapies for atherosclerosis.

Limitations:

• The review focuses primarily on specific proteins and pathways, which may not encompass the entire complexity of atherosclerosis.
• Clinical implications of the findings require further validation through experimental and clinical studies.

Conclusion:

Elucidating the immuno-vascular networks involved in atherosclerosis may lead to next-generation precision-targeted therapies.