Post‑translational modifications in atherosclerosis: Roles, mechanisms and therapeutic potential (Review)

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Biochemistry

Background:

• Atherosclerosis (AS) is a major cardiovascular disease driven by endothelial dysfunction, lipid accumulation, inflammation, and plaque instability.
• Protein post-translational modifications (PTMs) act as a crucial regulatory layer, translating cellular cues into functional protein changes.

Purpose of the Study:

• To review the roles of major PTMs in AS pathogenesis.
• To emphasize the integration of PTMs into disease-related regulatory networks.
• To evaluate the therapeutic potential of targeting PTMs in AS.

Main Methods:

• Comprehensive literature review of PTMs in atherosclerosis.
• Analysis of PTM integration into disease networks, including lysine lactylation and PTM crosstalk.
• Evaluation of therapeutic strategies targeting PTM-related enzymes and pathways.

Main Results:

• Major PTMs (lysine, cysteine modifications, phosphorylation, glycosylation, nitration, ADP-ribosylation) play significant roles in AS.
• Lysine lactylation links lactate metabolism to endothelial dysfunction and vascular cell changes.
• PTM crosstalk, such as SUMOylation-ubiquitination, coordinates key pathological processes like inflammasome activation.

Conclusions:

• PTMs are integral to AS pathogenesis, offering potential therapeutic targets.
• Targeting PTMs, including lysine lactylation and crosstalk, presents a promising avenue for AS treatment.
• Challenges remain in validating PTM effects, especially in human plaques, and bridging the translational gap.