关键词: Egr-1 HIF1α HOXA5 KLF4 MYD88 NANOG TLR decoy gene therapy intimal hyperplasia stem cell genes vein graft

Mesh : Animals Rabbits Oligodeoxyribonucleotides Hyperplasia NF-kappa B / genetics Transfection Toll-Like Receptors / genetics

来  源:   DOI:10.3390/ijms242115866   PDF(Pubmed)

Abstract:
The long-term patency of vein grafts is challenged by intimal hyperplasia. We sought to explore the intricate relationships between the transcription factor Egr-1, toll-like receptors (TLRs), and stem cell genes and also assessed oligodeoxynucleotide decoys (ODNs) as a strategy to prevent vein graft failures. A total of 42 New Zealand white rabbits were fed hyperlipidemic chow and classified into three groups. A double-stranded Egr-1 ODN was synthesized and infused in vein grafts prior to anastomosis with the common carotid artery. All vein grafts were retrieved at the conclusion of the predefined experimental period. Real-time quantitative polymerase chain reaction was performed to estimate expression patterns for several genes of interest. MYD88, TLR2-4, TLR8, NF-kB, TNF-α, IFNβ, and IFNγ; chemokines CCL4, CCL20, CCR2; numerous interleukins; and stem cell genes KFL4, NANOG, HOXA5, and HIF1α were universally downregulated in the ODN arm compared with the controls. By understanding these multifaceted interactions, our study offers actionable insights that may pave the way for innovative interventions in vascular reconstructions.
摘要:
静脉移植物的长期通畅受到内膜增生的挑战。我们试图探索转录因子Egr-1,toll样受体(TLRs),和干细胞基因,还评估了寡脱氧核苷酸诱饵(ODN)作为预防静脉移植物失败的策略。总共给42只新西兰大白兔喂食高脂血症食物,并分为三组。在与颈总动脉吻合之前,合成了双链Egr-1ODN并将其输注到静脉移植物中。在预定义的实验期结束时取回所有静脉移植物。进行实时定量聚合酶链反应以估计几种感兴趣基因的表达模式。MYD88,TLR2-4,TLR8,NF-kB,TNF-α,IFNβ,和IFNγ;趋化因子CCL4,CCL20,CCR2;许多白细胞介素;和干细胞基因KFL4,NANOG,与对照相比,HOXA5和HIF1α在ODN臂中普遍下调。通过理解这些多方面的互动,我们的研究提供了可行的见解,可能为血管重建的创新干预措施铺平道路.
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