The Role of the NF-κB Signaling Pathway in Atherosclerotic Plaque Rupture and Targeted Therapeutic Strategies

Area of Science:

• Cardiovascular Research
• Inflammation Biology
• Molecular Medicine

Background:

• Atherosclerosis (AS) involves chronic inflammation and lipid deposition, with residual inflammatory risk persisting despite lipid-lowering therapies.
• The nuclear factor-kappaB (NF-κB) signaling network, especially non-canonical pathways, is increasingly implicated in AS progression and plaque rupture.
• Current AS treatments focus on lipid reduction, but anti-inflammatory strategies are emerging as crucial.

Purpose of the Study:

• To review the shift in AS treatment strategies from lipid-lowering to anti-inflammatory approaches.
• To analyze the molecular mechanisms and epigenetic regulation of NF-κB signaling in AS.
• To explore therapeutic targeting of the NF-κB pathway for plaque stabilization and prevention of acute cardiovascular events.

Main Methods:

• Literature review focusing on the role of NF-κB signaling in atherosclerosis.
• Analysis of molecular activation mechanisms of canonical and non-canonical NF-κB pathways in AS.
• Summary of current drug development targeting NF-κB pathway components.

Main Results:

• Sustained activation of non-canonical NF-κB signaling drives AS plaque rupture.
• NF-κB pathway activation promotes pathological angiogenesis, vascular smooth muscle cell (VSMC) phenotypic switching, and macrophage dysfunction.
• This creates a cycle of inflammation and vascular damage, leading to cardiovascular events.

Conclusions:

• Targeting the NF-κB pathway presents a promising anti-inflammatory strategy for AS.
• Developing drugs targeting key kinases (e.g., NIK, IKKα) in the NF-κB pathway is crucial for stabilizing coronary plaques.
• Further research is needed to translate NF-κB-targeted therapies into clinical practice for preventing acute coronary syndromes.