Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Center of Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, and National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, 102300 Beijing, China.
Department of General Surgery & Pharmacy, The Affiliated Suqian First People's Hospital of Nanjing Medical University, 223800 Suqian, Jiangsu, China.
Front Biosci (Landmark Ed). 2024 Aug 19;29(8):288. doi: 10.31083/j.fbl2908288.
Vascular smooth muscle cell (VSMC) intimal migration, proliferation, and phenotypic transformation from a contractile to a synthetic state are hallmarks of the progression of atherosclerotic plaques. This study aims to explore the effects of exosomes derived from M2 macrophages (Exo) on the pathological changes of VSMCs in atherosclerosis (AS).
Cell Counting Kit-8 (CCK8) and wound healing assays were used to examine the impact of Exo on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, respectively. Western blotting was employed to analyze changes in the expression levels of contractile markers (e.g., alpha-smooth muscle actin [α-SMA]) and synthetic ones (e.g., osteopontin [OPN]) in VSMCs with or without Exo treatment. ApoE mice on a high fat diet were utilized to observe the effects of Exo on plaque progression and stability. Serial histopathological analysis was performed to elucidate the cellular mechanisms underlying the atheroprotective effects of Exo.
Compared with controls, Exo significantly inhibited PDGF-BB-induced VSMC proliferation, migration, and phenotypic transformation . In ApoE mice, Exo treatment led to a marked reduction in plaque size, necrotic core area, the CD68/α-SMA ratio, and matrix metalloproteinase 9 (MMP9) and OPN levels, while enhancing plaque stability.
Exo inhibit AS progression by regulating VSMC proliferation, migration, and phenotypic transformation.
血管平滑肌细胞（VSMC）内膜迁移、增殖以及从收缩型向合成型的表型转化是动脉粥样硬化斑块进展的标志。本研究旨在探讨来源于 M2 巨噬细胞的外泌体（Exo）对动脉粥样硬化（AS）中 VSMC 病理变化的影响。
采用细胞计数试剂盒（CCK8）和划痕愈合实验分别检测 Exo 对血小板衍生生长因子-BB（PDGF-BB）诱导的 VSMC 增殖和迁移的影响。采用 Western blot 分析 Exo 处理前后 VSMC 收缩型标志物（如α-平滑肌肌动蛋白[α-SMA]）和合成型标志物（如骨桥蛋白[OPN]）表达水平的变化。利用载脂蛋白 E（ApoE）基因敲除小鼠高脂饮食模型观察 Exo 对斑块进展和稳定性的影响。进行连续的组织病理学分析以阐明 Exo 发挥抗动脉粥样硬化作用的细胞机制。
与对照组相比，Exo 显著抑制 PDGF-BB 诱导的 VSMC 增殖、迁移和表型转化。在 ApoE 小鼠中，Exo 治疗导致斑块体积、坏死核心面积、CD68/α-SMA 比值以及基质金属蛋白酶 9（MMP9）和 OPN 水平显著降低，同时增强了斑块稳定性。
Exo 通过调节 VSMC 的增殖、迁移和表型转化抑制 AS 的进展。
