Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the Na+ -Ca2+ -Ca2+ /calmodulin-dependent protein kinase II-reactive oxygen species feedback.
Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the Na+ -Ca2+ -Ca2+ /calmodulin-dependent protein kinase II-reactive oxygen species feedback.
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定量系统模型阐明了心力衰竭的心律失常机制：Na -Ca2 -Ca2 /钙调蛋白依赖性蛋白激酶 II - 活性氧反馈的作用。
DOI：
10.1002/wsbm.1434
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Grandi,Eleonora
中科院分区：
文献类型：
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作者：
Morotti,Stefano;Grandi,Eleonora
定量系统建模旨在将不同研究领域的知识与描述生物机制和动力学的模型相结合，以更好地理解复杂的临床综合征。心力衰竭（HF）是一种慢性复杂心脏病，由结构或功能障碍损害心室充盈或射血能力引起。机械、结构、神经体液、代谢和电生理特性的高度交互和动态变化共同使衰竭的心脏容易发生心律失常，大约一半的心力衰竭死亡是由心律失常造成的。多尺度心脏建模和模拟整合了心力衰竭实验模型和患者的结构和功能数据，以提高我们对这种复杂心律失常综合征的机制理解。特别是，他们可以研究疾病引起的重塑如何改变电生理学、Ca2+和Na+处理、收缩和能量学的耦合，从而导致节律紊乱。 Ca2+/钙调蛋白依赖性蛋白激酶 II 在心力衰竭中表达和活性增强，成为调节这些不同子系统之间的反馈并促进心律失常发生的关键枢纽。本文分类为：生理学 > 健康和疾病中的哺乳动物生理学系统属性和过程模型 > 机械模型系统属性和过程模型 > 细胞模型系统属性和过程模型 > 器官、组织和过程生理模型
Quantitative systems modeling aims to integrate knowledge in different research areas with models describing biological mechanisms and dynamics to gain a better understanding of complex clinical syndromes. Heart failure (HF) is a chronic complex cardiac disease that results from structural or functional disorders impairing the ability of the ventricle to fill with or eject blood. Highly interactive and dynamic changes in mechanical, structural, neurohumoral, metabolic, and electrophysiological properties collectively predispose the failing heart to cardiac arrhythmias, which are responsible for about a half of HF deaths. Multiscale cardiac modeling and simulation integrate structural and functional data from HF experimental models and patients to improve our mechanistic understanding of this complex arrhythmia syndrome. In particular, they allow investigating how disease‐induced remodeling alters the coupling of electrophysiology, Ca2+and Na+handling, contraction, and energetics that lead to rhythm derangements. The Ca2+/calmodulin‐dependent protein kinase II, which expression and activity are enhanced in HF, emerges as a critical hub that modulates the feedbacks between these various subsystems and promotes arrhythmogenesis.This article is categorized under:Physiology > Mammalian Physiology in Health and DiseaseModels of Systems Properties and Processes > Mechanistic ModelsModels of Systems Properties and Processes > Cellular ModelsModels of Systems Properties and Processes > Organ, Tissue, and Physiological Models