Role Of MicroRNA And NF-κB Pathway In Atherosclerosis Induced By Chronic Intrauterine Hypoxia In Offspring

Objective 1.To inverstigate the effects of chronic intrauterine hypoxia on the growth and development and atherosclerosis in offsprings adulthood,based on the chronic intrauterine hypoxia model of golden hamster.2.To find related characteristic mi RNA by differentially expressed mi RNA in offspring aortic tissues of chronic intrauterine hypoxia and normal control.3.To preliminary explore the mechanism of the differentially expressed mi RNA-mediated NF-κB signaling pathway on atherosclerosis.Methods Sixteen pregnant golden hamsters were randomly divided into CIH group and normal controls group.The CIH group consisted of 8 rats exposed to a hypoxia condition from gestational days 5 to 17.Length,weight,total cholesterol,triglycerides were examined in offspring hamsters,thoracic aorta tissue sections were observed with light microscope and electron microscope.Differentially expressed mi RNA in aorta of offspring male hamsters were screened by digital gene expression profiles and identified by RT-PCT.Then the coresponding target genes were predicted,GO function analysis and KEGG Pathway analysis were performed.In combination with DGE results,pyrrolidine dithiocarbamate intervention was used,main proteins of NF-κB signaling pathway were evaluated by Western blot assay.Results 1.CIH can lead to fetal growth restriction(P <0.05),but low birth weight progenies will catch-up growth during lactation(P <0.05).2.CIH can induce early atherosclerosis pathological changes in the offspring adult hamsters,mainly including intima-media thickness and foam cell infiltration.3.CIH programmed to 19 differentially expressed mi RNA in aorta of offspring male hamsters,including 9 upregulated and 10 downregulated,target genes involved in a variety of metabolic enzymes and inflammatory cytokines.4.GO functional analysis and KEGG Pathway analysis showed differentially expressed mi RNA were significantly enriched in Insulin signaling pathway and NF-κB signaling pathway.5.CIH up-regulates the expression of NF-κB/p65 and NF-κB/p100(P <0.05),pyrrolidine dithiocarbamate can reduces atherosclerosis in offspring caused by chronic hypoxia.Conclusions CIH programmed to differentially expressed mi RNA in aorta of offspring male hamsters.Programming of enhanced inflammatory response-related signaling pathways might be the possible mechanism of CIH related atherosclerosis,especially the NF-κB signaling pathway.