Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the Na+-Ca2+-Ca2+/calmodulin-dependent protein kinase II-reactive oxygen species feedback

Stefano Morotti, Eleonora Grandi

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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 Disease Models of Systems Properties and Processes > Mechanistic Models Models of Systems Properties and Processes > Cellular Models Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models

Original languageEnglish (US)
JournalWiley Interdisciplinary Reviews: Systems Biology and Medicine
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • Cardiac arrhythmia
  • Heart failure
  • Mechanistic modeling

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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