BTEB2 knockdown suppresses neointimal hyperplasia in a rat artery balloon injury model
BTEB2 knockdown suppresses neointimal hyperplasia in a rat artery balloon injury model
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DOI：
10.3892/mmr.2011.438
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发表时间：
2011-05-01
影响因子：
3.4
通讯作者：
Tang, Bing
中科院分区：
文献类型：
--
作者：
Li, De;Ma, Shuangtao;Tang, Bing
基本转录元件结合蛋白2 （BTEB2）是血管平滑肌细胞（SMCs）增殖和表型变化的调节因子。本研究的目的是确定BTEB2敲低是否抑制球囊损伤诱导的新生内膜增生，这是由血管SMCs的增殖和表型改变引起的。我们发现，与Ad-LacZ治疗的未损伤动脉和血管相比，反义寡核苷酸（Ad-As-BTEB2）敲低BTEB2显著降低了内膜/中膜比率。BTEB2基因敲低可抑制体外培养血管SMCs的增殖，同时下调增殖细胞核抗原、血管紧张素11型受体和血小板源性生长因子BB的表达。BTEB2敲低导致分化标记平滑肌a-肌动蛋白上调，去分化标记胚胎平滑肌肌球蛋白重链下调。本研究提供了BTEB2在球囊损伤诱导的新生内膜增生中起关键作用的直接证据，而新生内膜增生与血管SMC增殖和表型调节密切相关。这项研究强调了BTEB2可能是预防血管介入后再狭窄的潜在靶点。
Basic transcription element-binding protein 2 (BTEB2) is a regulator of the proliferation and phenotypic changes of vascular smooth muscle cells (SMCs). The aim of the present study was to determine whether or not BTEB2 knockdown inhibits balloon injury-induced neointimal hyperplasia attributed to the proliferation and phenotypic changes of vascular SMCs. We found that the knockdown of BTEB2 with antisense oligonucleotides (Ad-As-BTEB2) significantly reduced the intima/media ratio compared to uninjured arteries and vessels treated with Ad-LacZ. Knockdown of BTEB2 suppresses the proliferation of cultured vascular SMCs, concurrent with the down-regulation of proliferating cell nuclear antigen, angiotensin 11 type 1 receptor and platelet-derived growth factor BB. In addition, BTEB2 knockdown caused the up-regulation of the differentiation marker smooth muscle a-actin and down-regulation of the dedifferentiation marker embryonic smooth muscle myosin heavy chain. The present study provides direct evidence that BTEB2 plays a critical role in balloon injury-induced neointimal hyperplasia, which is closely linked to vascular SMC proliferation and phenotypic modulation. This study highlights the fact that BTEB2 may be a potential target for the prevention of restenosis after vascular intervention.