Plasma Small Extracellular Vesicle-Carried miRNA-501-5p Promotes Vascular Smooth Muscle Cell Phenotypic Modulation-Mediated In-Stent Restenosis.
Plasma Small Extracellular Vesicle-Carried miRNA-501-5p Promotes Vascular Smooth Muscle Cell Phenotypic Modulation-Mediated In-Stent Restenosis.
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血浆小细胞外囊泡携带的 miRNA-501-5p 促进血管平滑肌细胞表型调节介导的支架内再狭窄
DOI：
10.1155/2021/6644970
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发表时间：
2021
影响因子：
--
通讯作者：
Chen SL
中科院分区：
文献类型：
--
作者：
Gao XF;Wang ZM;Chen AQ;Wang F;Luo S;Gu Y;Kong XQ;Zuo GF;Jiang XM;Ding GW;Chen Y;Ge Z;Zhang JJ;Chen SL
血管平滑肌细胞（VSMC）的表型调控在支架内再狭窄（ISR）的发生发展中起着重要作用，其发生机制仍是亟待解决的关键问题。本研究旨在探讨血浆小细胞外囊泡（sEV）在VSMC表型调节中的作用。应用差速超离心法从有或无ISR患者（ISR sEV）的血浆中分离sEV。ISR患者血浆sEV明显升高，VSMC收缩标志物α-SMA和Calponin表达减少，VSMC增殖增加。miRNA测序和qRT-PCR验证表明，与Ctl-sEV相比，miRNA-501- 5 p是血浆ISR-sEV中表达最高的miRNA。结果发现，ISR患者血浆中携带sEV的miRNA-501- 5 p水平显著升高，且血浆中携带sEV的miRNA-501- 5 p水平与再狭窄程度呈线性相关（R2 = 0.62）。抑制miRNA-501- 5 p可显著增加VSMC收缩标志物α-SMA和calponin的表达，抑制VSMC增殖和迁移;体内抑制miRNA-501- 5 p也可减弱大鼠颈动脉球囊损伤诱导的VSMC表型调节。在机制上，miRNA-501- 5 p通过靶向Smad 3促进血浆sEV诱导的VSMC增殖。值得注意的是，内皮细胞可能是miRNA-501- 5 p的主要来源。总之，这些发现表明，血浆sEV携带的miRNA-501- 5 p通过靶向Smad 3促进VSMC表型调节介导的ISR。
Vascular smooth muscle cell (VSMC) phenotypic modulation plays an important role in the occurrence and development of in-stent restenosis (ISR), the underlying mechanism of which remains a key issue needing to be urgently addressed. This study is designed to investigate the role of plasma small extracellular vesicles (sEV) in VSMC phenotypic modulation. sEV were isolated from the plasma of patients with ISR (ISR-sEV) or not (Ctl-sEV) 1 year after coronary stent implantation using differential ultracentrifugation. Plasma sEV in ISR patients are elevated markedly and decrease the expression of VSMC contractile markers α-SMA and calponin and increase VSMC proliferation. miRNA sequencing and qRT-PCR validation identified that miRNA-501-5p was the highest expressed miRNA in the plasma ISR-sEV compared with Ctl-sEV. Then, we found that sEV-carried miRNA-501-5p level was significantly higher in ISR patients, and the level of plasma sEV-carried miRNA-501-5p linearly correlated with the degree of restenosis (R2 = 0.62). Moreover, miRNA-501-5p inhibition significantly increased the expression of VSMC contractile markers α-SMA and calponin and suppressed VSMC proliferation and migration; in vivo inhibition of miRNA-501-5p could also blunt carotid artery balloon injury induced VSMC phenotypic modulation in rats. Mechanically, miRNA-501-5p promoted plasma sEV-induced VSMC proliferation by targeting Smad3. Notably, endothelial cells might be the major origins of miRNA-501-5p. Collectively, these findings showed that plasma sEV-carried miRNA-501-5p promotes VSMC phenotypic modulation-mediated ISR through targeting Smad3.
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影响因子：
21.3
作者：
Hergenreider, Eduard;Heydt, Susanne;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
DOI：
10.1161/atvbaha.119.312141
发表时间：
2019-06
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Wong D;Turner AW;Miller CL
通讯作者：
Miller CL
影响因子：
5.6
作者：
Pan, Ruijun;Cai, Wei;Zheng, Minhua
通讯作者：
Zheng, Minhua
DOI：
10.1161/atvbaha.110.218149
发表时间：
2011-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Chen J;Yin H;Jiang Y;Radhakrishnan SK;Huang ZP;Li J;Shi Z;Kilsdonk EP;Gui Y;Wang DZ;Zheng XL
通讯作者：
Zheng XL