LOC283683-NIPA1-BMPRII途径对胆固醇平衡和动脉粥样硬化的影响及机制研究

项目名称： LOC283683-NIPA1-BMPRII途径对胆固醇平衡和动脉粥样硬化的影响及机制研究

项目编号： No.81472009

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王前

作者单位： 南方医科大学

项目金额： 72万元

中文摘要： LncRNA在基因调控中起重要作用并与众多疾病相关，为了研究lncRNA对AS的影响，我们通过基因芯片筛选人正常动脉内膜与人动脉内膜斑块中差异表达的lncRNA和mRNA，发现斑块组织的lncRNA LOC283683下调，NIPA1上调而BMPRII下调。在巨噬细胞过表达LOC283683能下调NIPA1表达而上调BMPRII表达。在巨噬细胞过表达NIPA1能下调BMPRII表达。在巨噬细胞过表达LOC283683和NIPA1能分别促进和抑制细胞内胆固醇流出。因此我们提出LOC283683可能通过抑制NIPA1表达从而促进BMPRII表达，发挥促进巨噬细胞内胆固醇流出和抗AS作用。本项目拟通过增强LOC283683和/或NIPA1表达，观察LOC283683-NIPA1-BMPRII对胆固醇平衡和AS形成的影响并探讨相关机制，为确定此途径作为调控胆固醇平衡和防治AS新靶点提供科学依据。

中文关键词： 长链非编码RNA；NIPA1；蛋白；骨形态发生蛋白受体II；动脉粥样硬化；胆固醇

英文摘要： Long non-coding RNA (lncRNA) plays an important role in regulation of gene expression and is associated with many diseases. To investigate possible changes in lncRNA expression during atherosclerosis formation, we performed microarray analysis of normal arterial intima and advanced atherosclerotic plaque. The microarray analysis revealed that lncRNA LOC283683 levels and BMPRII levels were significantly down-regulated while NIPA1 levels were markedly up-regulated in advanced atherosclerotic plaque when compared with normal arterial intima. Furthermore, NIPA1 expression was inhibited while BMPRII expression was enhanced by overexpression of LOC283683 in macrophages. Moreover, BMPRII expression was inhibited by overexpression of NIPA1 in macrophages. In addition, cholesterol efflux was increased by overexpression of LOC283683 while reduced by overexpression of NIPA1 in macrophages. Thus, we hypothesize that atherosclerosis development can be affected by LOC283683-NIPA1-BMPRII pathway through regulating cholesterol homeostasis. In this project, we aim to explore the effect and mechanism of LOC283683-NIPA1-BMPRII pathway on cholesterol balance and atherosclerosis development by enhancing expression of LOC283683 and/or NIPA1. Therefore, our study may provide new scientific evidence to establish LOC283683-NIPA1-BMPRII pathway as a new target for regulation of cholesterol homeostasis and prevention of atherosclerosis.

英文关键词： lncRNA;NIPA1 protein;BMPRII;atherosclerosis;cholesterol