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Oxidant stress, inflammatory and autonomic pathways in the development of atrial fibrillation
Author(s) -
Van Wagoner David R
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.9.3
Subject(s) - atrial fibrillation , medicine , heart failure , cardiology , nadph oxidase , inflammation , oxidative stress
Atrial fibrillation (AF) affects more than 3 million Americans. AF promotes heart failure (HF) and is associated with increased risk of stroke and mortality. While AF promotes electrophysiologic changes in atrial myocytes and changes in the pathways of electrical activation, ion channel blockers have proved largely ineffective in treating or preventing AF. To identify the causes of AF, recent studies have focused on “upstream” pathways that precede its onset. Advanced age is the strongest risk factor for AF, but male gender, hypertension, valvular heart disease and HF also increase risk of AF. Hemodynamic stress increases atrial endothelin‐1 abundance, contributing to NADPH oxidase (NOX) expression and activity. NOX activity contributes to atrial electrophysiologic and structural remodeling that promotes persistent AF. Autonomic activation secondary to heart failure contributes to dysregulation of intracellular calcium handling and ectopic electrical activity. Both oxidant stress and autonomic activation promote systemic inflammation and inflammatory cell activation. Statins have been shown to have some antioxidant and anti‐inflammatory activity, but their impact on AF is limited. It remains to be determined whether other therapies that more specifically address upstream signaling pathways can help to prevent AF or improve the management of this common but vexing aging‐related condition.