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心肌梗死后患者血清来源的外泌体通过 miRNA-143/IGF-IR 通路促进血管生成。

Exosome Derived from Coronary Serum of Patients with Myocardial Infarction Promotes Angiogenesis Through the miRNA-143/IGF-IR Pathway.

机构信息

Department of Cardiovascular Disease, Cangzhou Central Hospital of Tianjin Medical University, Cangzhou, Hebei Province, People's Republic of China.

出版信息

Int J Nanomedicine. 2020 Apr 21;15:2647-2658. doi: 10.2147/IJN.S242908. eCollection 2020.

Abstract

PURPOSE

Myocardial ischemia-reperfusion injury primarily causes myocardial infarction (MI), which is manifested by cell death. Angiogenesis is essential for repair and regeneration in cardiac tissue after MI. In this study, we aimed to investigate the effect of exosomes derived from the serum of MI patients in angiogenesis and its related mechanism.

PATIENTS AND METHODS

Exosomes, isolated from serum, were collected from MI (MI-exosome) and control (Con-exosome) patients. After coculturing with human umbilical vein endothelial cells, MI-exosome promoted cell proliferation, migration, and tube formation.

RESULTS

The results revealed that the production and release of MI-exosome were associated with cardiomyocytes. Moreover, microarray assays demonstrated that miRNA-143 was significantly decreased in MI-exosome. Meanwhile, the overexpression and knockdown of miRNA-143 could inhibit and enhance angiogenesis, respectively. Furthermore, the effect of exosomal miRNA-143 on angiogenesis was mediated by its targeting gene, insulin-like growth factor 1 receptor (IGF-IR), and was associated with the production of nitric oxide (NO).

CONCLUSION

Taken together, exosomes derived from the serum of patients with MI promoted angiogenesis through the IGF-IR/NO signaling pathway. The results provide novel understanding of the function of exosomes in MI.

摘要

目的

心肌缺血再灌注损伤主要导致心肌梗死(MI),表现为细胞死亡。血管生成对于 MI 后心脏组织的修复和再生至关重要。本研究旨在探讨 MI 患者血清来源的外泌体在血管生成中的作用及其相关机制。

患者和方法

从 MI(MI-exosome)和对照(Con-exosome)患者的血清中分离出外泌体。与人脐静脉内皮细胞共培养后,MI-exosome 促进细胞增殖、迁移和管形成。

结果

结果表明,MI-exosome 的产生和释放与心肌细胞有关。此外,微阵列分析表明,MI-exosome 中 miRNA-143 的表达显著降低。同时,miRNA-143 的过表达和敲低分别抑制和增强了血管生成。此外,外泌体 miRNA-143 对血管生成的作用是通过其靶基因胰岛素样生长因子 1 受体(IGF-IR)介导的,与一氧化氮(NO)的产生有关。

结论

总之,MI 患者血清来源的外泌体通过 IGF-IR/NO 信号通路促进血管生成。这些结果为外泌体在 MI 中的功能提供了新的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1198/7183550/157c8eb65b3e/IJN-15-2647-g0001.jpg

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