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N-羧甲基赖氨酸通过 Vav1/Rac1 通路负调控泡沫细胞迁移。

N-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway.

机构信息

Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.

Department of Internal Medicine, Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi 214000, China.

出版信息

J Immunol Res. 2020 Feb 28;2020:1906204. doi: 10.1155/2020/1906204. eCollection 2020.

DOI:10.1155/2020/1906204
PMID:32190703
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7064830/
Abstract

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-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.

摘要

背景

巨噬细胞源性泡沫细胞在动脉粥样硬化中起核心作用，其最终命运包括细胞凋亡、促进血管炎症或迁移到其他组织。N-羧甲基赖氨酸（CML）是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。先前的研究表明，Vav1/Rac1 通路影响巨噬细胞细胞骨架和细胞迁移，但它在糖尿病动脉粥样硬化发病机制中的作用尚不清楚。

方法和结果

在这项研究中，我们使用了糖尿病足截肢患者和意外截肢患者的胫前腓骨血管样本，以及糖尿病 ApoE 小鼠模型和原代腹腔巨噬细胞，分别进行了组织学和细胞学检测。结果表明，糖尿病足截肢患者和糖尿病 ApoE 小鼠的动脉粥样硬化斑块大于对照组。抑制 Vav1/Rac1 通路可减少血管斑块并促进巨噬细胞向淋巴结迁移。Transwell 和划痕愈合实验表明，CML 抑制了巨噬细胞源性泡沫细胞的迁移能力。细胞骨架染色显示，糖基化终产物抑制泡沫细胞中片状伪足的形成，而抑制 Vav1/Rac1 通路则恢复了片状伪足的形成。

结论

CML 通过 Vav1/Rac1 通路抑制泡沫细胞从血管迁移，这一过程影响片状伪足的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/1e76ba114f0a/JIR2020-1906204.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/00cb649aff20/JIR2020-1906204.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/2512d186c591/JIR2020-1906204.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/25aafa1bd3bd/JIR2020-1906204.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/e5d283174c8e/JIR2020-1906204.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/1e76ba114f0a/JIR2020-1906204.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/00cb649aff20/JIR2020-1906204.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/2512d186c591/JIR2020-1906204.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/25aafa1bd3bd/JIR2020-1906204.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/e5d283174c8e/JIR2020-1906204.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528a/7064830/1e76ba114f0a/JIR2020-1906204.005.jpg

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