Atherosclerosis, a slowly progressing inflammatory disease, is characterized by the presence of monocyte‐derived macrophages. Interventions targeting the inflammatory characteristics of atherosclerosis hold promising potential. Although interleukin (IL)‐10 is widely acknowledged for its anti‐inflammatory effects, systemic administration of IL‐10 has limitations due to its short half‐life and significant systemic side effects. In this study, we aimed to investigate the effectiveness of an approach designed to overexpress IL‐10 in macrophages and subsequently introduce these genetically modified cells into ApoE−/− mice to promote atherosclerosis regression. We engineered RAW264.7 cells to overexpress IL‐10 (referred to as IL‐10M) using lentivirus vectors. The IL‐10M exhibited robust IL‐10 secretion, maintained phagocytic function, improved mitochondrial membrane potentials, reduced superoxide production and showed a tendency toward the M2 phenotype when exposed to inflammatory stimuli. IL‐10M can selectively target plaques in ApoE−/− mice and has the potential to reduce plaque area and necrotic core at both early and late stages of plaque progression. Moreover, there was a significant reduction in MMP9, a biomarker associated with plaque rupture, in IL‐10M‐treated plaques from both the early and late intervention groups. Additionally, the administration of IL‐10M showed no obvious side effects. This study serves as proof that cell therapy based on anti‐inflammatory macrophages might be a promising strategy for the intervention of atherosclerosis.

中文翻译：

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巨噬细胞过表达白细胞介素 10 靶向并预防动脉粥样硬化：斑块形成的消退和坏死核心的减少


动脉粥样硬化是一种缓慢进展的炎症性疾病，其特征是存在单核细胞衍生的巨噬细胞。针对动脉粥样硬化炎症特征的干预措施具有广阔的前景。尽管白细胞介素 (IL)-10 因其抗炎作用而被广泛认可，但由于其半衰期短和显着的全身副作用，全身给药 IL-10 具有局限性。在这项研究中，我们旨在研究一种在巨噬细胞中过度表达 IL-10 的方法的有效性，然后将这些转基因细胞引入 ApoE−/− 小鼠中以促进动脉粥样硬化消退。我们使用慢病毒载体改造RAW264.7细胞以过表达IL-10（称为IL-10M）。 IL-10M 表现出强劲的 IL-10 分泌，维持吞噬功能，改善线粒体膜电位，减少超氧化物产生，并在暴露于炎症刺激时表现出 M2 表型的趋势。 IL-10M 可以选择性地靶向 ApoE−/− 小鼠的斑块，并有可能在斑块进展的早期和晚期阶段减少斑块面积和坏死核心。此外，在早期和晚期干预组的 IL-10M 治疗斑块中，MMP9（一种与斑块破裂相关的生物标志物）显着减少。此外，IL-10M 的给药没有显示出明显的副作用。这项研究证明基于抗炎巨噬细胞的细胞疗法可能是干预动脉粥样硬化的一种有前途的策略。