SFB 1116: Master switches in cardiac ischemia

SFB 1116：心脏缺血的总开关

• 批准号: 236177352
• 金额: --
• 依托单位: Heinrich-Heine-Universität Düsseldorf
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/236177352?language=en
• 关键词: SFB; 1116; Master; switches; cardiac

The fundamental and prospective aim of the CRC 1116 “Master switches in cardiac ischemia” is to identify new targets, i.e. molecules, pathways and mechanisms that are critical for the acute and subacute response to myocardial ischemia, which we define as “master switches”. Importantly, the CRC 1116 considers systemic cross talk of ischemic cardiac injury and systemic inflammatory responses, metabolic comorbidities (obesity, insulin resistance, type 2 diabetes (T2DM)) and anemia. The CRC 1116 is organized into two conceptual areas. Project group A, “Intracellular and Cellular Effectors”, will address key aspects of pathophysiologic responses to cardiac ischemia such as ion channel remodeling, sarcomere function in the remote myocardium, role of p27 and telomerase reverse transcriptase (TERT) in mitochondria, platelet functions beyond aggregation, growth factor signaling and modulators of G-protein coupled receptor signaling and their role for immune cell responses and cardiac myocyte responses, respectively, as well as in-depth analysis of the protective function of cardiac hyaluronan-rich matrix.In project group B “Metabolic Effectors and Systemic Interference” the focus lies on the complex cross talk between infarct healing and cardiac adaptation and systemic effector systems and comorbidities. The projects in project group B address (i) mechanisms regulating the inflammatory response after cardiac ischemia such as the adenosine-interleukin-6 axis and co-stimulatory molecules to modulate T cell responses (ii) mechanisms underlying the confounding effects in patients with insulin resistance, obesity and T2DM, the so far unknown role of brown adipose tissue and of sphingosine 1 phosphate in myocardial ischemia and T2DM. Potential clinical translation is expected from investigating the confounding effects of T2DM on remote ischemic conditioning in a large animal model. Using translational approaches the impact of insulin resistance, non-alcoholic fatty liver disease with ectopic lipid deposition and of T2DM in ST elevation myocardial infarction (STEMI) will be studied in patients. Thereby the CRC1116 will provide new targets (master switches) and/or treatment options taking into account the specific pathophysiological context determined by comorbidities and other systemic interferences. The identification of these “master switches” in the acute and subacute phase after cardiac ischemia will be useful to better stratify patients to targeted therapies and ultimately positively affect their long-term outcome.

CRC 1116“心肌缺血中的主开关”的基本和前瞻性目标是确定新的靶点，即对心肌缺血的急性和亚急性反应至关重要的分子、途径和机制，我们将其定义为“主开关”。重要的是，CRC 1116考虑了缺血性心脏损伤和全身炎症反应的全身串扰、代谢合并症（肥胖、胰岛素抵抗、2型糖尿病（T2 DM））和贫血。CRC 1116分为两个概念领域。项目组A，“细胞内和细胞效应器”，将讨论心肌缺血的病理生理反应的关键方面，如离子通道重塑，远端心肌中的肌节功能，线粒体中p27和端粒酶逆转录酶（TERT）的作用，血小板聚集以外的功能，生长因子信号传导和G蛋白偶联受体信号传导的调节剂及其分别对免疫细胞应答和心肌细胞应答的作用，在项目组B“代谢效应物和全身性干扰”中，重点在于梗死愈合和心脏适应性与全身效应物系统和合并症之间的复杂串扰。项目组B的项目涉及（i）调节心肌缺血后炎症反应的机制，如腺苷-白细胞介素-6轴和调节T细胞反应的共刺激分子（ii）胰岛素抵抗、肥胖和T2 DM患者中混杂效应的潜在机制，棕色脂肪组织和1-磷酸鞘氨醇在心肌缺血和T2 DM中迄今未知的作用。通过在大型动物模型中研究T2 DM对远程缺血性预处理的混杂效应，预期可能的临床转化。使用转化方法，将在患者中研究胰岛素抵抗、非酒精性脂肪肝伴异位脂质沉积和T2 DM对ST段抬高心肌梗死（STEMI）的影响。因此，CRC 1116将提供新的靶点（主开关）和/或治疗选择，同时考虑到由合并症和其他全身干扰确定的特定病理生理背景。在心肌缺血后的急性和亚急性阶段识别这些“主开关”将有助于更好地将患者分层到靶向治疗，并最终积极影响其长期结局。