Nε-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway
Nε-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway
复制标题
N epsilon-羧甲基-赖氨酸通过 Vav1/Rac1 途径负向调节泡沫细胞迁移
DOI：
10.1155/2020/1906204
复制
发表时间：
2020-02-28
影响因子：
4.1
通讯作者：
Wang, Zhongqun
中科院分区：
文献类型：
--
作者：
Bao, Zhengyang;Zhang, Lili;Wang, Zhongqun
背景。巨噬细胞衍生的泡沫细胞在动脉粥样硬化中起着核心作用，它们的最终命运包括凋亡、促进血管炎症或迁移到其他组织。N - epsilon-Carboxymethyl-lysine （CML）是晚期糖基化终产物的关键活性成分，可诱导泡沫细胞形成和凋亡。既往研究表明，Vav1/Rac1通路影响巨噬细胞骨架和细胞迁移，但其在糖尿病动脉粥样硬化发病中的作用尚不清楚。方法与结果。在本研究中，我们使用糖尿病足截肢患者和意外截肢患者的胫腓骨前血管样本，分别使用糖尿病ApoE（-/-）小鼠模型和原代腹膜巨噬细胞进行组织学和细胞学检查。结果显示，糖尿病足截肢患者和糖尿病ApoE（-/-）小鼠的动脉粥样硬化斑块均大于对照组。抑制Vav1/Rac1通路可减少血管斑块，促进巨噬细胞向淋巴结的迁移。Transwell和伤口愈合实验显示，CML抑制巨噬细胞来源的泡沫细胞的迁移能力。细胞骨架染色显示，晚期糖基化终产物抑制泡沫细胞板足的形成，抑制Vav1/Rac1通路恢复板足的形成。结论。CML通过Vav1/Rac1途径抑制泡沫细胞从血管迁移，这一过程影响板足的形成。
Background. Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. N epsilon-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic atherosclerosis is unknown. Methods and Results. In this study, we used anterior tibiofibular vascular samples from diabetic foot amputation patients and accident amputation patients, and histological and cytological tests were performed using a diabetic ApoE(-/-) mouse model and primary peritoneal macrophages, respectively. The results showed that the atherosclerotic plaques of diabetic foot amputation patients and diabetic ApoE(-/-) mice were larger than those of the control group. Inhibition of the Vav1/Rac1 pathway reduced vascular plaques and promoted the migration of macrophages to lymph nodes. Transwell and wound healing assays showed that the migratory ability of macrophage-derived foam cells was inhibited by CML. Cytoskeletal staining showed that advanced glycation end products inhibited the formation of lamellipodia in foam cells, and inhibition of the Vav1/Rac1 pathway restored the formation of lamellipodia. Conclusion. CML inhibits the migration of foam cells from blood vessels via the Vav1/Rac1 pathway, and this process affects the formation of lamellipodia.