lncRNA NR_027921/HCC-1/NF-κB新途径对炎症反应和动脉粥样硬化的影响及机制研究

长链非编码RNA（LncRNA）在调控炎症反应和AS中起重要作用，但lncRNA NR_027921对炎症反应和AS的影响未见相关报道。预实验发现AS斑块组织中NR_027921表达下调而HCC-1表达上调，且冠心病病人血清中HCC-1表达升高，过表达NR_027921能抑制HCC-1、NF-κB和炎症因子表达水平，过表达HCC-1能上调NF-κB和炎症因子表达水平。据此我们提出NR_027921通过下调HCC-1表达从而抑制NF-κB表达，进而抑制炎症反应和AS进展。本项目拟①研究NR_027921调节HCC-1的机制；②研究HCC-1调节NF-κB的机制；③体内实验观察NR_027921和HCC-1对AS病变的影响；④观察HCC-1在AS疾病中的诊断价值。项目的完成将为确定lncRNA NR_027921/HCC-1/NF-κB途径作为调控炎症反应和AS防治新靶点提供科学依据。

Long non-coding RNA (LncRNA) plays an important role in the regulation of inflammation and atherosclerosis, but the effects of lncRNA NR_027921 on inflammation and atherosclerosis have not been explored. Our preliminary experimental results showed that the expression level of lncRNA NR_027921 was down-regulated while that of Hemofiltrate CC chemokine-1 (HCC-1) was up-regulated in atherosclerosis plaque tissues. In addition, the expression level of HCC-1 was increased in serum of patients with coronary heart disease. Overexpression of lncRNA NR_027921 significantly inhibited the expression levels of HCC-1, nuclear factor kappa B (NF-κB) and inflammatory factors. And overexpression of HCC-1 promoted the expression levels of NF-κB and inflammatory factors. Therefore, we hypothesize that lncRNA NR_027921 may inhibit the expression of NF-κB by reducing HCC-1 expression, thereby inhibiting the progression of inflammation and atherosclerosis. In this study, we aim to investigate the mechanism of lncRNA NR_027921 on HCC-1 expression, the mechanism of HCC-1 on NF-κB expression, the effects of lncRNA NR_027921 and HCC-1 on atherosclerosis lesions in vivo and the diagnostic value of HCC-1 in coronary heart disease. Thus, our study may provide new scientific evidence to establish lncRNA NR_027921/HCC-1/NF-κB pathway as a new target for regulation of inflammation, prevention and treatment of atherosclerosis.