Brd2及其抑制分子I-BET影响急性心肌梗死预后的转化医学和基因网络研究

项目名称： Brd2及其抑制分子I-BET影响急性心肌梗死预后的转化医学和基因网络研究

项目编号： No.81470571

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： 周颖玲

作者单位： 广东省心血管病研究所

项目金额： 68万元

中文摘要： 2ACU目前认为炎症学说是急性心肌梗死（AMI）发生发展的主要理论基础之一。近年来溴结构域亚家族主要成员Brd2及其抑制分子I-BET在炎症中的角色引起关注。申请人前期研究证实Brd2在动脉内皮存在功能表达，炎症上调Brd2表达而加重炎症反应,且Brd2与NF-κB p65亚基相关联;I-BET可减轻人动脉内皮细胞表面的白细胞粘附，下调主要炎症基因表达。鉴于Brd2和NF-κB分别与炎症密切关联，而Brd2和I-BET在AMI预后中的作用及机制目前还不明确，本研究拟通过动物模型观察I-BET对AMI预后的影响,研究梗死后心肌的权重基因共表达网络关系，并识别Brd2和I-BET影响AMI预后的信号基因模块，挖掘关键基因与信号通路；在心肌细胞水平上，通过NEO网络边定向方法分析关键调控基因与NF-κB的交互作用，初步揭示Brd2影响AMI预后的分子机制，提供AMI防治的新靶点。

中文关键词： 急性心肌梗死；Brd2；I-BET；WGCNA

英文摘要： Inflammation has been regarded as one of the main theoretical basis in the development of acute myocardial infarction(AMI) by far.In recent years, Brd2 ,the main member of BET subfamily, and its inhibitor I-BET,has gained much attention in the evolution of inflammation.We have previously demonstrated that Brd2 is functionally expressed in arterial endothelium,and inflammation functionally upregulates the expression of Brd2 and excerbates the inflammatory responses in turn,yet Brd2 links to p65 subunit;I-BET could alleviate leukocytes adhesion on human arterial endothelium,and downregulate the expression of main inflammatory genes.In the light of the close correlation of inflammation with Brd2 and NF-κB，respectively,whereas the interaction and mechanisms of Brd2 and I-BET remains to be elucidated,this study aims to investigate the influence of I-BET on the prognosis of AMI,to discuss the weighted gene co-expression network in post-infarct myocardium,to identify signalling gene modules through which Brd2 and I-BET affect the prognosis of AMI,and to explore hub genes and signalling pathways;We will also analyze the interaction between hub genes and NF-κB by network edge orienting software,disclosing the mechanisms by which Brd2 modulates the prognosis of AMI,revealing new targets for AMI therapy.

英文关键词： acute myocardial infarction;Brd2;I-BET;WGCNA