Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.
نویسندگان
چکیده
BACKGROUND Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation. METHODS AND RESULTS For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-β. CONCLUSIONS This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation.
منابع مشابه
Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies?
Atrial fibrillation (AF) is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF d...
متن کاملProtective effects of simvastatin on atrioventricular node during simulated experimental atrial fibrillation in vitro
Introduction: Recent evidence has indicated that statins can reduce the incidence of both supraventricular and ventricular arrhythmias with various mechanisms. The primary goal of the present study was to determine direct protective role of simvastatin in modifying concealed conduction and the zone of concealment in a simulated model of atrial fibrillation (AF) in an isolated atrioventricula...
متن کاملIncidence of Atrial Fibrillation after Coronary Artery Bypass Graft Surgery and Its Risk Factors in Shiraz, Iran during 2017-18
Background and Objectives: Atrial fibrillation is one of the most common disorientations after coronary artery bypass graft surgery and can affect the chance of survival in the first year after surgery. The present study aimed to determine the incidence of atrial fibrillation after coronary artery bypass graft surgery and its risk factors. Methods: This cross-sectional study was performed on...
متن کاملTherapeutic implications of atrial fibrillation mechanisms: can mechanistic insights be used to improve AF management?
Atrial fibrillation (AF) is a very common clinical problem, and presently available treatment options are suboptimal. A tremendous amount has been learned over the past 10 years about the atrial substrates that support sustained AF at the tissue, ionic and molecular levels. This understanding of the fundamental mechanisms underlying AF has opened up a variety of new, rationally-based therapeuti...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation. Arrhythmia and electrophysiology
دوره 9 5 شماره
صفحات -
تاریخ انتشار 2016