Emerging insights into inflammation-driven atherosclerosis: immune cell mechanisms

Atherosclerosis is a chronic inflammatory disease marked by the deposition of lipids, fibrous components, and calcification in the major arteries. The process is initiated by endothelial activation, which increases vascular permeability, promotes leukocyte adhesion, and leads to the migration of inflammatory cells into the arterial wall. These events trigger vascular constriction and activate inflammatory pathways, together promoting atheromatous plaque development. This review integrates emerging concepts in the immune cascade, detailing how recruited immune cells such as macrophages, T cells, B cells, dendritic cells (DCs), and neutrophils interact to sustain inflammation within developing plaques, as revealed by single-cell omics approaches. In addition, we discuss novel ideas, such as phenotypic switching of vascular smooth muscle cells into macrophage-like foam cells and the systemic effects of clonal haematopoiesis. Finally, we explore how systemic and environmental factors, including gut microbiota, epigenetic changes, hypertension, diabetes, obesity, and smoking, maintain a state of trained immunity and meta-inflammation that exacerbates disease, thus providing a conceptual framework for targeting inflammatory axes in future therapeutic strategies.