Immunology of atherosclerosis as an inflammatory disease: rethinking the dynamic immunoinflammatory activity beneath stability.

Abstract

Introduction: Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and fibrous components within the arterial wall. While traditionally considered a lipid-driven process, growing evidence suggests that immune mechanisms play a central role in all stages of atherogenesis.

Areas covered: This review summarizes the most relevant evidence supporting the immunoinflammatory basis of plaque development, progression, and destabilization. Both innate and adaptive immune responses contribute to endothelial dysfunction, immune cell recruitment, cytokine production, and the activation of inflammasome pathways, which amplify vascular inflammation. Crucially, the interplay between inflammation and thrombosis, termed thromboinflammation, plays a pivotal role in plaque instability and clinical events.

Expert opinion: We critically examine the limitations of the classic dichotomy between stable and unstable plaques, proposing instead a tripartite classification: active, dormant, and inactive plaques, analogous to the states of volcanic activity. Even clinically 'stable' plaques may exhibit silent yet ongoing immunometabolic and thromboinflammatory activity, contributing to residual cardiovascular risk. Advanced imaging, molecular diagnostics, and inflammation-sensitive biomarkers (e.g. high-sensitivity C-reactive protein, IL-6) can help detect subclinical plaque activity. Finally, the concept of 'thromboinflammaging' emphasizes the impact of age-related immune dysregulation on vascular pathology. This evolving paradigm supports immunomodulation as a cornerstone in precision cardiovascular medicine.