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Cardiovascular Drugs and Therapy

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01-04-2016 | ORIGINAL ARTICLE

Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Regulate the Phenotype of Smooth Muscle Cells to Limit Intimal Hyperplasia

Authors: Rong Liu, Hong Shen, Jian Ma, Leiqing Sun, Meng Wei

Published in: Cardiovascular Drugs and Therapy | Issue 2/2016

Abstract

Purpose

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) play important roles in the reduction of inflammation in multiple disease models. However, their role in vein graft (VG) remodeling is undefined. We aimed to investigate the effect of EVs from adipose MSCs (ADMSC-EVs) on VG intimal hyperplasia and to explore the possible mechanisms.

Methods

After generation and characterization of control-EVs and ADMSC-EVs in vitro, we investigated their effect on the proliferation and migration of vascular smooth muscle cells (VSMCs) in vitro. Next, we established a mouse model of VG transplantation. Mice underwent surgery and received control-EVs or ADMSC-EVs by intraperitoneal injection every other day for 20 days. VG remodeling was evaluated after 4 weeks. We also assessed the effect of ADMSC-EVs on macrophage migration and inflammatory cytokine expression.

Results

Significant inhibitory effects of ADMSC-EVs on in vitro VSMC proliferation (p < 0.05) and migration (p < 0.05) were observed compared with control-EVs. The extent of intimal hyperplasia was significantly decreased in ADMSC-EV-treated mice compared with control-EV-treated mice (26 ± 8.4 vs. 45 ± 9.0 μm, p < 0.05). A reduced presence of macrophages was observed in ADMSC-EV-treated mice (p < 0.05). Significantly decreased expression of inflammatory cytokines interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) was also found in the ADMSC-EV-treated group (both p < 0.05). In addition, phosphorylation of Akt, Erk1/2, and p38 in VGs was decreased in the ADMSC-EV-treated group.

Conclusions

We demonstrated that ADMSC-EVs exert an inhibitory effect on VG neointima formation by regulating VSMC proliferation and migration, macrophage migration, inflammatory cytokine expression, and the related signaling pathways.

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Title: Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Regulate the Phenotype of Smooth Muscle Cells to Limit Intimal Hyperplasia
Authors: Rong Liu
Hong Shen
Jian Ma
Leiqing Sun
Meng Wei
Publication date: 01-04-2016
Publisher: Springer US
Published in: Cardiovascular Drugs and Therapy / Issue 2/2016
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-015-6630-5

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Purpose

Methods

Results

Conclusions

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