The role of Ca/calmodulin dependent protein kinase II (CaMKII) in the heart for triggering and maintenance of atrial fibrillation in diabetes mellitus

Ca/钙调蛋白依赖性蛋白激酶 II (CaMKII) 在心脏中对糖尿病心房颤动的触发和维持的作用

• 批准号: 321175284
• 负责人: Professor Lars Maier, since 8/2019
• 金额: --
• 依托单位: Klinik und Poliklinik für Innere Medizin II
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/321175284?language=en
• 关键词: role; Ca; calmodulin; dependent; protein

Diabetes mellitus (DM) is a worldwide epidemic that causes numerous cardiovascular diseases and increases mortality in patients. DM is also an independent risk factor for atrial fibrillation (AF), while the mechanisms of DM-associated AF are poorly understood. Along with the clinical importance of DM concerning increased morbidity and mortality, DM is also a pivotal social and economic problem. My previous studies and work from other groups suggest CaMKII plays a critical role in triggering and maintenance of AF. Therefore, in this research proposal I would like to study the role of oxidized CaMKII as compared to mitochondrial CaMKII for AF triggering and maintenance in DM. I will use a range of mouse models, but also human atrial heart tissue. To further decipher the mechanistic pathways I will use both in-vitro and in-vivo techniques. My hypotheses include defects of intracellular Ca homeostasis and upstream-mechanisms of CaMKII activation, but also adverse atrial remodeling, which promotes the maintenance of AF. My translational research proposal aims at identifying unknown disease pathways as well as first applications of new therapeutic concepts.

糖尿病（DM）是一种世界性流行病，可引起多种心血管疾病并增加患者的死亡率。糖尿病也是心房颤动（AF）的独立危险因素，而糖尿病相关AF的机制尚不清楚。沿着糖尿病发病率和死亡率增加的临床重要性，糖尿病也是一个关键的社会和经济问题。我以前的研究和其他小组的工作表明，CaMKII在AF的触发和维持中起着关键作用。因此，在本研究中，我想研究氧化CaMKII与线粒体CaMKII相比在糖尿病AF触发和维持中的作用。我将使用一系列小鼠模型，但也包括人类心房心脏组织。为了进一步破译机制途径，我将使用体外和体内技术。我的假设包括细胞内钙稳态和CaMKII激活的上游机制的缺陷，但也不利的心房重构，促进AF的维持。我的翻译研究建议旨在确定未知的疾病途径以及新的治疗概念的首次应用。