microRNA-155靶向调控血管平滑肌细胞NoxA1在动脉粥样硬化中的作用机制

批准号:
81700316
项目类别:
青年科学基金项目
资助金额:
20.0 万元
负责人:
严文文
依托单位:
学科分类:
H0205.冠状动脉性心脏病
结题年份:
2020
批准年份:
2017
项目状态:
已结题
项目参与者:
王乐民、陈治松、解元、金芸、虞宇楠、罗容春
国基评审专家1V1指导 中标率高出同行96.8%
结合最新热点,提供专业选题建议
深度指导申报书撰写,确保创新可行
指导项目中标800+,快速提高中标率
微信扫码咨询
中文摘要
动脉粥样硬化(AS)是冠心病的病变基础,其血管内膜病变机制未完全阐明。巨噬细胞中miR-155上调致基因沉默可使炎症因子释放增加、胆固醇外流减少,增加AS风险,但在血管平滑肌细胞 (VSMC)中的表达调控及与粥样硬化的关注很少。NADPH-ROS-VSMC通路异常是粥样斑块演变过程的重要诱因,预实验表明miR-155可与VSMC中编码NADPH亚单位的基因NoxA1结合,抑制NoxA1的表达和翻译。根据miR-155在低氧刺激下促进细胞凋亡,提出“miR-155使NoxA1基因表达下调,抑制VSMC过度增殖、延缓AS进程”的设想,通过miR-155转染VSMC入大鼠早期AS模型,观察粥样斑块进展与miR-155调控的VSMC增殖迁移的关系;动脉损伤小鼠模型检测NoxA1基因及蛋白表达,为早期特异性检测VSMC增殖以预判动脉内膜病变、诊断动脉粥样硬化和新型靶向药物的开发提供理论基础。
英文摘要
Atherosclerosis is the fundamental pathogenesis of coronary arterial diseases. The mechanism of intimal lesion is not fully elucidated. Previous studies have confirmed that miR-155 induced gene silence in macrophage will increase inflammatory cytokines release and reduce macrophage cholesterol efflux, thereby increasing the risk of atherosclerosis. However, few studies focused on miR-155 regulation in vascular smooth muscle cells (VSMC) and its relationship with atherosclerosis. NADPH-ROS-VSMC pathway abnormality was an important risky factor in atherosclerosis process and our pilot studies indicated that miR-155 has complementary binding sites with gene NoxA1 that encoding NADPH oxidase subunit.According to miR-155’s characteristic of promoting cell apoptosis induced by hypoxia, hypothesis "miR-155 expression down-regulates NoxA1 gene expression,thereby inhibiting VSMC over proliferation and attenuating atherosclerosis" was proposed. Envisaged by miR-155 transfected VSMC injecting into rat model with early atherosclerosis to observe the relationship between plaque formation and miR-155 regulated VSMC proliferation and migration; detection of NoA1 gene and protein expression via arterial injury mouse model, which may provide theoretical evidence for early detection of arterial neointima hyperplasia, diagnosis and prevention of atherosclerotic diseases and new targeted drugs development.
动脉粥样硬化(AS)是冠心病的病变基础,其血管内膜病变机制未完全阐明。巨噬细胞中miR-155上调致基因沉默可使炎症因子释放增加、胆固醇外流减少,增加AS风险,但在血管平滑肌细胞 (VSMC)中的表达调控及与粥样硬化的关注很少。NADPH-ROS-VSMC通路异常是粥样斑块演变过程的重要诱因,预实验表明miR-155可与VSMC中编码NADPH亚单位的基因NoxA1结合,抑制NoxA1的表达和翻译。本课题旨在初步证明“miR-155使NoxA1基因表达下调,抑制VSMC过度增殖、延缓AS进程”的设想,通过miR-155转染VSMC入小鼠早期AS模型,观察粥样斑块进展与miR-155调控的VSMC增殖迁移的关系;动脉损伤小鼠模型检测NoxA1基因及蛋白表达,为早期特异性检测VSMC增殖以预判动脉内膜病变、诊断动脉粥样硬化和新型靶向药物的开发提供理论基础。. 研究结果显示经转染miR-155VSMC处理的AS小鼠,其颈动脉、腹主动脉血管内膜病变程度要显著轻于空白对照组和miR-155抑制剂组,内膜增生厚度、炎性细胞浸润以及NADPH、NoxA1免疫荧光染色较其余各组均有明显改善,符合课题的研究假设,即增加外源性miR-155的VSMC可使AS通路的关键基因表达减弱,具有一定程度改善AS发生发展的作用。. 本研究通过miR-155转染VSMC入大鼠早期AS模型,观察粥样斑块进展与miR-155调控的VSMC增殖迁移的关系;动脉损伤小鼠模型检测NoxA1基因及蛋白表达,除了建立相关成熟疾病动物模型,还可为早期特异性检测VSMC增殖以预判动脉内膜病变、诊断动脉粥样硬化和新型靶向药物的开发提供理论基础。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Establishment of exercise intensity for patients with chronic heart failure equivalent to anaerobic threshold based on 6-minute walking test
基于6分钟步行试验建立慢性心力衰竭患者相当于无氧阈值的运动强度
DOI:10.21037/apm-20-265
发表时间:2020-09-01
期刊:ANNALS OF PALLIATIVE MEDICINE
影响因子:--
作者:Luo,Qian;Li,Congcong;Shen,Yuqin
通讯作者:Shen,Yuqin
MiR-155 acts as an inhibitory factor in atherosclerosis-associated arterial pathogenesis by down-regulating NoxA1 related signaling pathway in ApoE-/- mouse
MiR-155 通过下调 ApoE-/- 小鼠中 NoxA1 相关信号通路,充当动脉粥样硬化相关动脉发病机制的抑制因子
DOI:10.21037/cdt-20-518
发表时间:2021-02-01
期刊:CARDIOVASCULAR DIAGNOSIS AND THERAPY
影响因子:2.4
作者:Tang,Yu;Song,Haoming;Yan,Wenwen
通讯作者:Yan,Wenwen
mRNA expression disturbance of complement system related genes in acute arterial thrombotic and paroxysmal atrial fibrillation patients
急性动脉血栓和阵发性房颤患者补体系统相关基因mRNA表达紊乱
DOI:10.21037/apm.2020.04.18
发表时间:2020
期刊:Annals of Palliative Medicine
影响因子:--
作者:Siwan Wen;Wenwen Yan;Lemin Wang
通讯作者:Lemin Wang
国内基金
海外基金
