Cooperation of the two interferon-inducible transcription factors STAT1 and IRF1 in the pathogenesis of acute myocardial infarction

两种干扰素诱导转录因子STAT1和IRF1在急性心肌梗死发病机制中的协同作用

• 批准号: 168454758
• 负责人: Professor Dr. Thomas Meyer
• 金额: --
• 依托单位: Klinik für Psychosomatische Medizin und Psychotherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/168454758?language=en
• 关键词: Cooperation; two; interferon; inducible; transcription

One of the major therapeutic challenges of modern cardiology is to design efficacious strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair mechanisms following acute myocardial infarction. Inflammation, including the recruitment of neutrophils and macrophages to the infarcted area, is a hallmark feature of myocardial ischemia which contributes to myocardial injury. The inflammatory reaction triggered by the local release of cytokines such as interferons is a prerequisite for tissue repair but also the cause of scar formation in the ischemic heart tissue. The two interferon-dependent transcription factors STAT1 (signal transducer and activator of transcription 1) and IRF1 (interferon-regulatory factor 1) are involved in the regulation of inflammatory reactions. However, their roles in the infarcted myocardium following permanent or transient occlusion of a coronary artery have not been systematically investigated in an organismic context. Using transgenic mouse models, we aimed at studying the functional cooperativity of the two interferon-inducible transcription factors in the control of inflammatory infiltrates in infarcted areas. From the proposed project, we expect insights into the pathogenesis of myocardial infarction which may help to identify novel targets for future pharmacological interventions.

现代心脏病学的主要治疗挑战之一是设计有效的策略，旨在最大限度地减少急性心肌梗死后的心肌坏死和优化心脏修复机制。炎症，包括中性粒细胞和巨噬细胞向梗死区域的募集，是导致心肌损伤的心肌缺血的标志性特征。由细胞因子如干扰素的局部释放引发的炎症反应是组织修复的先决条件，但也是缺血心脏组织中瘢痕形成的原因。两种干扰素依赖性转录因子STAT 1（信号转导和转录激活因子1）和IRF 1（干扰素调节因子1）参与炎症反应的调节。然而，他们的作用，在梗死心肌永久或短暂闭塞冠状动脉尚未系统地研究在器官的背景下。利用转基因小鼠模型，我们旨在研究两种干扰素诱导的转录因子在控制梗死区炎症浸润中的功能协同性。从拟议的项目中，我们期望深入了解心肌梗死的发病机制，这可能有助于确定未来药物干预的新靶点。