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 language | English (US) |
|---|---|
| Journal | Wiley Interdisciplinary Reviews: Systems Biology and Medicine |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- Cardiac arrhythmia
- Heart failure
- Mechanistic modeling
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
Cite this
Quantitative systems models illuminate arrhythmia mechanisms in heart failure : Role of the Na+-Ca2+-Ca2+/calmodulin-dependent protein kinase II-reactive oxygen species feedback. / Morotti, Stefano; Grandi, Eleonora.
In: Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Quantitative systems models illuminate arrhythmia mechanisms in heart failure
T2 - Role of the Na+-Ca2+-Ca2+/calmodulin-dependent protein kinase II-reactive oxygen species feedback
AU - Morotti, Stefano
AU - Grandi, Eleonora
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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
AB - 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
KW - Cardiac arrhythmia
KW - Heart failure
KW - Mechanistic modeling
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UR - http://www.scopus.com/inward/citedby.url?scp=85050638015&partnerID=8YFLogxK
U2 - 10.1002/wsbm.1434
DO - 10.1002/wsbm.1434
M3 - Article
C2 - 30015404
AN - SCOPUS:85050638015
JO - Wiley Interdisciplinary Reviews: Systems Biology and Medicine
JF - Wiley Interdisciplinary Reviews: Systems Biology and Medicine
SN - 1939-5094
ER -