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Identification of candidate genes linking systemic inflammation to atherosclerosis; results of a human in vivo LPS infusion study

机译:鉴定将全身性炎症与动脉粥样硬化联系起来的候选基因;体内LPS输液研究的结果

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Background It is widely accepted that atherosclerosis and inflammation are intimately linked. Monocytes play a key role in both of these processes and we hypothesized that activation of inflammatory pathways in monocytes would lead to, among others, proatherogenic changes in the monocyte transcriptome. Such differentially expressed genes in circulating monocytes would be strong candidates for further investigation in disease association studies. Methods Endotoxin, lipopolysaccharide (LPS), or saline control was infused in healthy volunteers. Monocyte RNA was isolated, processed and hybridized to Hver 2.1.1 spotted cDNA microarrays. Differential expression of key genes was confirmed by RT-PCR and results were compared to in vitro data obtained by our group to identify candidate genes. Results All subjects who received LPS experienced the anticipated clinical response indicating successful stimulation. One hour after LPS infusion, 11 genes were identified as being differentially expressed; 1 down regulated and 10 up regulated. Four hours after LPS infusion, 28 genes were identified as being differentially expressed; 3 being down regulated and 25 up regulated. No genes were significantly differentially expressed following saline infusion. Comparison with results obtained in in vitro experiments lead to the identification of 6 strong candidate genes ( BATF, BID, C3aR1, IL1RN, SEC61B and SLC43A3 ) Conclusion In vivo endotoxin exposure of healthy individuals resulted in the identification of several candidate gene s through which systemic inflammation links to atherosclerosis.
机译:背景技术动脉粥样硬化与炎症密切相关已被广泛接受。单核细胞在这两个过程中都起着关键作用,我们假设单核细胞中炎症途径的激活会导致单核细胞转录组的促动脉粥样硬化。循环单核细胞中这种差异表达的基因将成为疾病关联研究中进一步研究的强有力候选者。方法向健康志愿者中注入内毒素,脂多糖(LPS)或生理盐水。分离,处理单核细胞RNA并将其与Hver 2.1.1斑点cDNA微阵列杂交。通过RT-PCR确认关键基因的差异表达,并将结果与​​我们小组获得的体外数据进行比较以鉴定候选基因。结果所有接受LPS的受试者均经历了预期的临床反应,表明成功的刺激。 LPS输注后1小时,鉴定出11个差异表达的基因。 1下调和10上调。 LPS输注后四个小时,鉴定出28个基因是差异表达的。 3下调和25上调。输注盐水后没有基因显着差异表达。与在体外实验中获得的结果进行比较,可以鉴定出6个强候选基因(BATF,BID,C3aR1,IL1RN,SEC61B和SLC43A3)结论结论健康个体的体内内毒素暴露导致鉴定了几个候选基因,通过这些候选基因,全身性炎症与动脉粥样硬化有关。

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