PMID- 26650931 OWN - NLM STAT- MEDLINE DCOM- 20170224 LR - 20181202 IS - 1573-7241 (Electronic) IS - 0920-3206 (Linking) VI - 30 IP - 2 DP - 2016 Apr TI - Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Regulate the Phenotype of Smooth Muscle Cells to Limit Intimal Hyperplasia. PG - 111-8 LID - 10.1007/s10557-015-6630-5 [doi] AB - 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 mum, 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. FAU - Liu, Rong AU - Liu R AD - Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai, 200233, China. FAU - Shen, Hong AU - Shen H AD - Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai, 200233, China. FAU - Ma, Jian AU - Ma J AD - Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai, 200233, China. FAU - Sun, Leiqing AU - Sun L AD - Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai, 200233, China. FAU - Wei, Meng AU - Wei M AD - Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai, 200233, China. weimeng6h@126.com. LA - eng PT - Journal Article PL - United States TA - Cardiovasc Drugs Ther JT - Cardiovascular drugs and therapy JID - 8712220 RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-6) SB - IM MH - Adipose Tissue/metabolism/*pathology MH - Animals MH - Cell Movement/physiology MH - Cell Proliferation/physiology MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - Disease Models, Animal MH - Endothelium, Vascular/metabolism/pathology MH - Extracellular Vesicles/metabolism/*pathology/physiology MH - Humans MH - Hyperplasia/metabolism/*pathology MH - Inflammation/metabolism/pathology MH - Interleukin-6/metabolism MH - Male MH - Mesenchymal Stem Cells/metabolism/*pathology/physiology MH - Muscle, Smooth, Vascular/metabolism/pathology MH - Myocytes, Smooth Muscle/metabolism/*pathology MH - Neointima/metabolism/pathology MH - Phenotype MH - Phosphorylation/physiology MH - Signal Transduction/physiology OTO - NOTNLM OT - Adipose-derived mesenchymal stem cells OT - Extracellular vesicles OT - Migration OT - Proliferation OT - Vascular smooth muscle cells OT - Vein grafts EDAT- 2015/12/10 06:00 MHDA- 2017/02/25 06:00 CRDT- 2015/12/10 06:00 PHST- 2015/12/10 06:00 [entrez] PHST- 2015/12/10 06:00 [pubmed] PHST- 2017/02/25 06:00 [medline] AID - 10.1007/s10557-015-6630-5 [pii] AID - 10.1007/s10557-015-6630-5 [doi] PST - ppublish SO - Cardiovasc Drugs Ther. 2016 Apr;30(2):111-8. doi: 10.1007/s10557-015-6630-5.