Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin

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.

Tongxinluo capsule as a multi-functional traditional Chinese medicine in treating cardiovascular disease: A review of components, pharmacological mechanisms, and clinical applications

“…Endovascular proliferation is a natural repair process after vascular damage, but excessive proliferation can lead to the occurrence of vascular restenosis. Endometrial proliferation of blood vessels originates from the excessive proliferation, migration, and phenotypic transformation of smooth muscle cells in the intima of blood vessels, which are stimulated by local or circulatory oxidative stress and inflammatory factors [ 182 , 183 ]. The entire process includes endothelial damage, platelet aggregation, inflammatory cell infiltration, smooth muscle cell proliferation and migration to the subintima, etc [ 184 ] Endovascular hyperplasia is the central link in the pathological process of vascular remodeling.…”

G6PD maintains the VSMC synthetic phenotype and accelerates vascular neointimal hyperplasia by inhibiting the VDAC1–Bax-mediated mitochondrial apoptosis pathway

“…The dynamic switching of the VSMC phenotype from contractile to synthetic is a common pathogenesis of various vascular remodeling diseases (VRDs) [ 3 – 5 ] and is typically characterized by a loss of contractile function, replacement of proproliferative and antiapoptotic factors, and increased secretion of extracellular matrix [ 6 – 9 ]. In particular, when vascular endothelial damage or postoperative restenosis occurs, an imbalance between excessive VSMC proliferation and insufficient apoptosis may lead to the abnormal accumulation of vascular intimal cells, which can cause atherosclerosis or restenosis [ 10 – 12 ]. A classic rat model for studying vascular injury has shown that the synthetic peptide MRSP effectively inhibits neointimal hyperplasia by promoting VSMC apoptosis [ 13 ].…”