PDF(Pubmed)
Abstract：
Neointimal hyperplasia is a pathological vascular remodeling caused by abnormal proliferation and migration of subintimal vascular smooth muscle cells (VSMCs) following intimal injury. There is increasing evidence that tRNA-derived small RNA (tsRNA) plays an important role in vascular remodeling. The purpose of this study is to search for tsRNAs signature of neointima formation and to explore their potential functions. The balloon injury model of rat common carotid artery was replicated to induce intimal hyperplasia, and the differentially expressed tsRNAs (DE-tsRNAs) in arteries with intimal hyperplasia were screened by small RNA sequencing and tsRNA library. A total of 24 DE-tsRNAs were found in the vessels with intimal hyperplasia by small RNA sequencing. In vitro, tRF-Glu-CTC inhibited the expression of fibromodulin (FMOD) in VSMCs, which is a negative modulator of TGF-β1 activity. tRF-Glu-CTC also increased VSMC proliferation and migration. In vivo experiments showed that inhibition of tRF-Glu-CTC expression after balloon injury of rat carotid artery can reduce the neointimal area. In conclusion, tRF-Glu-CTC expression is increased after vascular injury and inhibits FMOD expression in VSMCs, which influences neointima formation. On the other hand, reducing the expression of tRF-Glu-CTC after vascular injury may be a potential approach to prevent vascular stenosis.
摘要：
新生内膜增生是血管内膜损伤后内膜下血管平滑肌细胞(VSMCs)异常增殖和迁移引起的病理性血管重塑。越来越多的证据表明，tRNA衍生的小RNA（tsRNA）在血管重塑中起着重要作用。这项研究的目的是寻找新内膜形成的tsRNAs特征并探索其潜在的功能。复制大鼠颈总动脉球囊损伤模型,诱导内膜增生,通过小RNA测序和tsRNA文库筛选动脉内膜增生中差异表达的tsRNAs(DE-tsRNAs)。通过小RNA测序，在内膜增生的血管中共发现24个DE-tsRNA。体外，tRF-Glu-CTC抑制VSMC中纤调素（FMOD）的表达，它是TGF-β1活性的负调节剂。tRF-Glu-CTC也增加VSMC增殖和迁移。体内实验表明，在大鼠颈动脉球囊损伤后，抑制tRF-Glu-CTC的表达可以减少新生内膜面积。总之,血管损伤后tRF-Glu-CTC表达增加并抑制VSMC中FMOD表达，影响新内膜的形成。另一方面,降低血管损伤后tRF-Glu-CTC的表达可能是预防血管狭窄的潜在方法。
