Ijaz Adil, Yarlagadda Bhavya, Orecchioni Marco
Immunology Center of Georgia, Augusta University, Augusta, GA, United States.
Department of Pharmacology and Toxicology, Augusta University, Augusta, GA, United States.
Front Cardiovasc Med. 2025 May 2;12:1589629. doi: 10.3389/fcvm.2025.1589629. eCollection 2025.
Atherosclerosis is a complex immuno-metabolic disease characterized by lipid accumulation and chronic inflammation within arterial walls, leading to cardiovascular events such as stroke and myocardial infarction. Central to the disease are arterial plaques initiated by modified low-density lipoproteins (LDL), particularly oxidized LDL, deposited in the arterial intima. This deposition activates tissue-resident macrophages (TRMs), inducing a lipid-loaded "foamy" phenotype. Additionally, endothelial dysfunction promotes monocyte recruitment, differentiation into macrophages, and further foam cell formation. Foamy macrophages were initially identified as anti-inflammatory but have recently shown dual functionality, possibly depending on the disease stage and phenotype. Recent mouse and human studies also identified subsets of "foamy" macrophages with both pro and anti-inflammatory features. This review examines "foamy" macrophage complex roles and phenotypic diversity in atherosclerosis, emphasizing their potential as therapeutic targets to reduce inflammation and slow disease progression.
动脉粥样硬化是一种复杂的免疫代谢疾病，其特征是动脉壁内脂质积聚和慢性炎症，导致中风和心肌梗死等心血管事件。该疾病的核心是由修饰的低密度脂蛋白（LDL），特别是氧化LDL沉积在动脉内膜引发的动脉斑块。这种沉积激活组织驻留巨噬细胞（TRM），诱导脂质负载的“泡沫”表型。此外，内皮功能障碍促进单核细胞募集、分化为巨噬细胞，并进一步形成泡沫细胞。泡沫巨噬细胞最初被认为具有抗炎作用，但最近显示出双重功能，这可能取决于疾病阶段和表型。最近的小鼠和人类研究还确定了具有促炎和抗炎特征的“泡沫”巨噬细胞亚群。本文综述探讨了“泡沫”巨噬细胞在动脉粥样硬化中的复杂作用和表型多样性，强调了它们作为减少炎症和减缓疾病进展的治疗靶点的潜力。
