Inflammatory drivers of carotid atherosclerosis: signaling pathways, immune cells, and plaque stability

Background Carotid atherosclerosis (CAS; herein referring to carotid atherosclerotic disease, to be distinguished from carotid artery stenting, which shares the same abbreviation) is a primary driver of ischemic stroke, with inflammation playing a central role in its pathogenesis from plaque initiation to rupture. However, the complex regulatory network governing this inflammatory process remains to be fully elucidated. Purpose This review comprehensively reviews the molecular and cellular inflammatory mechanisms underlying CAS, focusing on key signaling pathways, inflammatory mediators, and immune cell populations, to identify potential targets for therapeutic intervention. As a narrative review, it does not follow a formal systematic-search protocol. Key findings We delineate the hierarchical activation of core signaling cascades—including the central NF-κB pathway, the MAPK and JAK/STAT modules, and the NLRP3 inflammasome—which collectively orchestrate a pro-inflammatory milieu. This network drives the expression of critical mediators (e.g., TNF-α, IL-1β, MMPs) and sculpts the behavior of lesional immune cells. Specifically, the imbalance between pro-inflammatory M1 macrophages together with Th1/Th17 effector T cells, vs. anti-inflammatory M2 macrophages and Tregs emerges as a key determinant of plaque stability. Conclusion and Implications: The pathogenesis of CAS is governed by an intricate, multi-level inflammatory network. A detailed understanding of this network, particularly the crosstalk between signaling pathways and immune cell plasticity, provides a rationale for novel precision therapies. Targeting specific nodes within this network, rather than broad immunosuppression, holds promise for stabilizing high-risk plaques and reducing the burden of cerebrovascular events.