Electrophysiology Scientific Core 2

SC2项目总结 心房颤动(房颤)是最常见的心律失常，也是心血管死亡和死亡的主要危险因素 卒中。由于肥胖和人口年龄的增加，房颤的发病率进一步增加，这与 与房颤的风险和进展有关。尽管房颤的诊断和管理取得了重大进展，但治疗 临床结果仍然很差，距离上一次发现房颤药物已经过去了十多年。这个 这个PPG应用程序的总体目标是使用遗传/基因组发现来确定预防和治疗 房颤的治疗策略，并向临床应用发展。我们的中心假设是，增加 了解涉及心房意志遗传、代谢和结构变化的分子机制 使我们能够为更安全和更有效的治疗策略确定可能的目标。科学核心2 (SC2)：电生理学核心将支持PPG和测试计划假设的总体目标，如 目标1.常规和可靠的心电数据采集，用于连续评估房颤的进展和 Burden，目标2：连接细胞的小鼠心房和工程心脏组织(EHT)的光学标测 房颤的病理生理学机制，目标3：酶法分离小鼠心房肌细胞 电生理、离子通道和钙循环研究。总的来说，分离的心肌细胞研究结合了 光学标测将在细胞病理生理学、原位房颤和 房颤在连续心电中的进展。我们将利用此核心的功能和专业知识来实现 项目研究人员系统地将电生理和细胞发现与基因 观察。这可以评估心房对新陈代谢或其他疾病的敏感性差异。 项目将作为房颤启动和进展的重要贡献者进行研究的压力源。重要的是 使用Core获取和分析心电、光学标测(鼠标心房和EHTS)，以及 分离的心肌细胞中钙离子、动作电位和离子通道动力学的特征确保一致性 将加强这一PPG的个别项目的方法。此外，代谢动力学 在这里在电生理上下文中测量的，将补充在代谢中测量的相同 背景(科学核心1)。此核心将提供深入的智力投入，以支持以下项目 实验设计、实验执行和实验协调，以及数据收集的集中化，从而 促进项目之间的互动和整合，而不仅仅是提供服务。最后，这个核心 消除重复劳动并优化人员、设备和用品的使用，从而使所有 这一PPG项目以有组织和具有成本效益的方式实现其科学目标。总而言之， 这一核心为项目提供的服务将有助于促进对房颤病理生理学的理解， 从而支持了PPG确定房颤和房颤的预防和治疗策略的主要目标 推动其临床应用。

SC2 PROJECT SUMMARY Atrial fibrillation (AF) is the most common arrhythmia and a major risk factor for cardiovascular mortality and stroke. Incidence of AF is further increasing due to the rise in obesity and age of the population, factors closely related to AF risk and progression. Despite significant advances in AF diagnosis and management, treatment and clinical outcomes remain poor and more than a decade has passed since the last AF drug discovery. The overall goal of this PPG application is to use genetic/genomic findings to identify preventative and therapeutic strategies for AF and develop them towards clinical application. Our central hypothesis is that increasing the understanding of molecular mechanisms involved in genetic, metabolic and structural changes in the atria will allow us to pinpoint possible targets for safer and more effective therapeutic strategies. Scientific Core 2 (SC2): Electrophysiology Core will support the overall goal of the PPG and test program hypotheses as follows: Aim 1. Routine and reliable acquisition of ECG data for serial assessment of AF progression and burden, Aim 2: Optical mapping of mice atria and engineered heart tissue (EHT) for linking cellular pathophysiology with mechanisms of AF, Aim 3: Enzymatic isolation of mouse atrial myocytes for electrophysiologic, ion channel and Ca2+ cycling studies. Collectively, the isolated myocyte studies combined with optical mapping will provide important mechanistic links between cellular pathophysiology, AF in situ, and the progresion of AF in serial ECGs. We will leverage the capabilities and expertise of this Core to allow Project investigators to systematically integrate electrophysiological and cellular findings with genetic observations. This allows an assessment of differences in susceptibility of the atria to metabolic or other stressors that Projects will be studying as important contributors to AF initiation and progression. Importantly, use of the Core for the acquisition and analysis of ECGs, optical mapping (mouse atria and EHTs), and characterization of Ca2+, action potential, and ion channel dynamics in isolated myocytes ensures uniform methodology that will strengthen the individual Projects of this PPG. Furthermore, metabolic dynamics measured in an electrophysiological context herein, will complement the same measured in a metabolic context (Scientific Core 1). This Core will provide in-depth intellectual input to support Projects with experimental design, execution and coordination of experiments, and centralization for data gathering, thereby promoting interaction and integration between Projects beyond merely providing a service. Finally, this core eliminates duplication of effort and optimizes the use of personnel, equipment, and supplies, which enables all Projects on this PPG to achieve their scientific goals in an organized and cost-efficient manner. In sum, the services provide by this core to the Projects will help advance the understanding of the pathophysiology of AF, thereby supporting the main goal of this PPG to identify preventive and therapeutic strategies for AF and advance them towards clinical application.