血管平滑肌
细胞生物学
微泡
新生内膜
新生内膜增生
信号转导
生物
内皮干细胞
化学
分子生物学
体外
小RNA
医学
内科学
内分泌学
生物化学
再狭窄
支架
基因
平滑肌
作者
Bo Li,Guangyao Zang,Wei Zhong,Rui Chen,Yue Zhang,Ping Yang,Jinchuan Yan
标识
DOI:10.1016/j.biopha.2019.109593
摘要
Activated endothelial cells (ECs) play an important role in the development of atherosclerosis (AS) because they form neointima resulting from abnormal vascular smooth muscle cell (VSMC) hyperplasia. TET2 was recently reported as a major regulator of the phenotypic switch of VSMCs, and it also protects ECs from noxious stimuli and represses inflammation in AS. The purpose of the present study is to determine whether activation of CD137 signaling can regulate the function of VSMCs by altering endothelial TET2 expression and to explore the potential mechanisms. VSMCs were isolated from C57BL/6 J mice, and the influence of ECs on VSMCs was analyzed using a co-culture system. Western blotting was used to detect the protein expression levels of TET2 and CD9, CD81, and CD63 as well as VSMC phenotypic markers. RT-PCR was performed to detect the TET2 mRNA levels. EdU proliferation assay and transwell migration assay were employed to assess the functions of VSMCs. EXO-spin kits were used to extract and purify exosomes. Transmission electron microscopy and nanoparticle tracking analysis were applied to characterize exosomes. ECs transduced with the TET2-overexpression lentivirus showed that the activation of endothelial CD137 signaling decreased TET2 expression and the TET2 content in exosomes. EC-derived exosomes were internalized by VSMCs, which inhibited phenotypic switching in vitro and neointimal formation in vivo. However, exosomes derived from CD137-activated ECs exhibited weakened protective effects on VSMCs. In conclusion, activation of endothelial CD137 signaling attenuated the repressive effects of EC-derived exosomes on platelet-derived growth factor (PDGF)-BB-induced phenotypic switching of VSMCs and neointimal formation after carotid injury.
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