Cardiac fibrosis and arrhythmogenesis: the road to repair is paved with perils

Autor: James N. Weiss, Zhilin Qu, Thao P. Nguyen
Rok vydání: 2013
Předmět:
Source-sink mismatch
Heart disease
Cardiac fibrosis
Medical Physiology
Arrhythmias
Cardiorespiratory Medicine and Haematology
Cardiovascular
Regenerative Medicine
Ventricular tachycardia
Cardiac arrhythmia
Afterdepolarization
Membrane Potentials
Fibrosis
2.1 Biological and endogenous factors
Medicine
Myocyte
Aetiology
Excitation Contraction Coupling
Effective refractory period
Gap Junctions
Cell Differentiation
Source–sink mismatch
Extracellular Matrix
Heart Disease
Cardiology
Reentry
Cardiology and Cardiovascular Medicine
Cardiac
medicine.medical_specialty
Article
Heart Conduction System
Internal medicine
Animals
Humans
Molecular Biology
Heart Disease - Coronary Heart Disease
Myofibroblast
Wound Healing
business.industry
Myocardium
Arrhythmias
Cardiac
Dispersion of refractoriness
Fibroblasts
medicine.disease
Myocardial Contraction
Good Health and Well Being
Cardiovascular System & Hematology
business
Neuroscience
Zdroj: Nguyen, TP; Qu, Z; & Weiss, JN. (2014). Cardiac fibrosis and arrhythmogenesis: The road to repair is paved with perils. Journal of Molecular and Cellular Cardiology, 70, 83-91. doi: 10.1016/j.yjmcc.2013.10.018. UCLA: Retrieved from: http://www.escholarship.org/uc/item/0612p58c
ISSN: 1095-8584
DOI: 10.1016/j.yjmcc.2013.10.018.
Popis: In the healthy heart, cardiac myocytes form an electrical syncytium embedded in a supportive fibroblast-rich extracellular matrix designed to optimize the electromechanical coupling for maximal contractile efficiency of the heart. In the injured heart, however, fibroblasts are activated and differentiate into myofibroblasts that proliferate and generate fibrosis as a component of the wound-healing response. This review discusses how fibroblasts and fibrosis, while essential for maintaining the structural integrity of the heart wall after injury, have undesirable electrophysiological effects by disrupting the normal electrical connectivity of cardiac tissue to increase the vulnerability to arrhythmias. We emphasize the dual contribution of fibrosis in altering source-sink relationships to create a vulnerable substrate while simultaneously facilitating the emergence of triggers such as afterdepolarization-induced premature ventricular complexes-both factors combining synergistically to promote initiation of reentry. We also discuss the potential role of fibroblasts and myofibroblasts in directly altering myocyte electrophysiology in a pro-arrhythmic fashion. Insight into these processes may open up novel therapeutic strategies for preventing and treating arrhythmias in the setting of heart disease as well as avoiding potential arrhythmogenic consequences of cell-based cardiac regeneration therapy. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signaling in Myocardium.". © 2013 Elsevier Ltd. All rights reserved.
Databáze: OpenAIRE
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